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Magnesium dietary manipulation and recovery of function following controlled cortical damage in the rat


Magnesium Research. Volume 21, Number 1, 29-37, march 2008, original article

DOI : 10.1684/mrh.2008.0128

Summary  

Author(s) : Michael R Hoane, David R Gilbert, Adrianne B Barbre, Stacy A Harrison , Restorative Neuroscience Laboratory, Brain and Cognitive Science Program, Department of Psychology, Southern Illinois University, Carbondale, IL, USA.

Summary : Previous research has shown that dietary magnesium (Mg2+) deficiency prior to injury worsens recovery of function and that systemic administration of Mg2+ pre or post-injury significantly improves functional recovery. The purpose of the present study was to determine if manipulations in dietary Mg2+ would alter functional recovery following unilateral cortical injuries. Two weeks prior to injury, rats were placed on a customized diet enriched with Mg2+, deficient in Mg2+, or on a standard Mg2+ diet. Rats were then prepared with unilateral cortical contusion injuries (CCI) of the sensorimotor cortex. Two days following CCI, rats were tested on a battery of sensorimotor (vibrissae-forelimb placing and bilateral tactile adhesive removal tests), as well as the acquisition of reference memory in the Morris water maze. Serum analysis for Mg2+ prior to injury showed a diet-dependent modulation in levels. The Mg2+-enriched diet showed significantly higher levels of serum Mg2+ compared to the normal diet and the Mg2+-deficient diet showed significantly lower levels compared to the Mg2+-normal diet. On the placing and tactile removal tests Mg2+ deficiency significantly worsened recovery compared to the Mg2+-enriched and Mg2+-normal diet conditions. There were no statistically significant differences between the Mg2+-normal and Mg2+-enriched diets on the sensorimotor tests. On the acquisition of reference memory there were no significant difference between diet conditions; however, the Mg2+-deficient diet showed a trend toward impaired performance compared to the other diet conditions. The Mg2+-deficient diet resulted in a larger lesion cavity compared to the other diet conditions. These findings suggest that dietary Mg2+ modulates recovery of function.

Keywords : diet, behavior, magnesium, neuroprotection, sensorimotor, TBI, recovery of function

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ARTICLE

Auteur(s) : Michael R Hoane, David R Gilbert, Adrianne B Barbre, Stacy A Harrison

Restorative Neuroscience Laboratory, Brain and Cognitive Science Program, Department of Psychology, Southern Illinois University, Carbondale, IL, USA

It is well established that Mg2+ is essential for maintaining normal cellular functions such as glycolysis [1], maintaining membrane structure and function [2], protein synthesis and DNA replication [3, 4]. Mg2+ also plays a vital role in the pathophysiological events that occur following injury to the central nervous system (CNS). One of these events is the disruption of normal Mg2+ homeostasis, which has been shown to be very detrimental. Vink and colleagues were the first to identify the disruption of Mg2+ homeostasis following CNS injury [5-7]. These studies have shown that fluid percussion injury (FPI) produced a rapid and severe decline in intra- and extracellular Mg2+ levels, which correlated significantly with the severity of the behavioral deficits observed following injury [5-8]. Heath and Vink have also shown that after severe impact-acceleration injury intracellular levels of free Mg2+ decline for four days post-injury and reach pre-injury levels again by the sixth day [9].

Mg2+ pharmacotherapy has been found to be an effective treatment in models of ischemia, FPI and cortical lesions. For example, it has been shown that administration of magnesium chloride (MgCl2) following focal cortical injuries significantly improved behavioral outcome and reduced the amount of lesion induced tissue damage [10]. It has also been shown that MgCl2 facilitated behavioral recovery following lesions that produce chronic impairments. MgCl2 induced recovery of forelimb placing following large cortical injuries that produced chronic impairments in untreated animals [11, 12]. Similarly, previous research has found that rats treated with daily injections of Mg2+ prior to an electrolytic lesion of the sensorimotor cortex (SMC) exhibited improved recovery of function when compared to those treated with saline [13]. Administration of magnesium sulphate (MgSO4) or MgCl2 has also been shown to improve functional outcome following FPI and diffuse axonal injury [5, 9, 14-19].

Given the fact that Mg2+ is a vital nutrient it might be expected that manipulation of dietary Mg2+ levels would have an impact on recovery of function following brain injury. A hallmark study by McIntosh and colleagues administered a Mg2+-deficient diet to rats for 14 days prior to FPI [5]. It was found that this diet reduced brain Mg2+ levels by 15% and resulted in a 53% mortality in the Mg2+-deficient group. It was also found that this diet significantly impaired the functional neuroscore assessment for 4 weeks following the injury. A Mg2+-deficient diet has also been shown to exacerbate alcohol-induced stroke fatalities [20]. Furthermore, several recent studies have shown that Mg2+ deficiency impairs fear conditioning. In these studies, a Mg2+-deficient diet (2-3 weeks) resulted in significant memory deficits in both contextual and cued conditioning tests; as well as increasing N-methyl-d-aspartate (NMDA) hyperfunction [21, 22]. This hyperfunctioning of the NMDA receptor should result in worsened behavioral outcome following TBI. Although, it has been shown that Mg2+ deficiency prior to injury worsened behavioral outcome it has yet to be determined how generalizable this effect is. For example, does it disrupt multiple behavioral systems (sensorimotor, motor or cognitive) and what is the neuropathological effect? Furthermore, can a Mg2+-enriched diet improve functional outcome when fed prior to injury?

The purpose of the present experiment was to examine the effect of dietary Mg2+ manipulation on recovery of function. Rats were placed on one of three different diets (Mg2+-normal, Mg2+-enriched, or Mg2+-deficient) for 2 weeks prior to receiving cortical injuries. Behavioral testing was conducted to assess sensorimotor and cognitive performance. This study will aid in the understanding of the relationship between Mg2+ dietary manipulations and behavioral outcome following brain injury.

Materials and methods

Subjects

Forty male Sprague-Dawley rats (weighing 275-350 g) were used as subjects. All experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee. Rats were maintained on a standard 12-h light/dark cycle with food and water available ad libitum.

Diet Manipulation

Experimental diets were purchased from Harlan TEKLAD (Madison, WI). The Mg2+-deficient diet (TD02373) was formulated with 0.0 g/kg of MgO. The Mg2+-normal diet (TD94253) was formulated with 1.02 g/kg of MgO. The Mg2+-enriched diet (TD02372) was formulated with 9.95 g/kg of MgO. All rats were placed onto their formulated diets 2 weeks prior to injury and were allowed to feed and drink ad libitum. All behavioral testing and anatomical analyses were conducted without knowledge of the diet assignment. Following surgery all animals were placed back onto normal rodent diets.

Serum Mg2+ analysis

Immediately prior to injury, blood was collected from the tail vein to be used for the determination of serum Mg2+ levels. Samples were frozen and shipped to a clinical laboratory for analysis using the ACE® magnesium reagent and NExCT™ clinical chemistry system (Schiapparelli Biosystems, Inc., Fairfield, NJ, USA).

Surgery

The surgical procedure was performed using aseptic procedures and conditions. Animals were anesthetized with a cocktail of ketamine (90 mg/kg, i.p.) and xylazine (10 mg/kg, i.p.) and then prepared for surgery [23]. When the animal became unresponsive (no ocular or pedal reflexes) it was shaved and scrubbed with 70% alcohol followed by betadine and placed in a stereotaxic device. A midline scalp incision was made in the skin and underlying fascia. A circular craniotomy (5.0 mm) was then performed with a Dremel hand drill and a specially designed drill bit that prevented damaging the meninges or cortical tissue. The craniotomy was unilateral and centered over the cortical region containing the sensorimotor cortex (-0.5 mm posterior and 3.0 mm lateral to bregma). The contusion injury was produced using a sterile, stainless steel impactor tip (3.0 mm diameter) attached to a piston activated with compressed air. The impactor tip was positioned above the cortex and upon activation (2.75 m/s), made contact with the cortex for 0.5 s, resulting in a 2.5 mm compression of the cortex. It should be noted that the impactor tip did not actually penetrate the cortex, or the meninges, but only momentarily compressed the tissue. Following the contusion, the incision was closed with nylon suture material. The animals were maintained on a heating pad (37°C) until they showed locomotive behavior and were then returned to their home cage. Sham animals were prepped for surgery, anesthetized, placed into the stereotaxic device, given a midline scalp incision and craniotomy, sutured and allowed to recover.

Behavioral analysis

Vibrissae- forelimb placing

This test measures sensorimotor dysfunction following cortical injury and has been described in detail [24]. Each forelimb was independently tested for placing reactions by touching the vibrissae to a Plexiglas surface. Testing was conducted on post-operative days 2, 4, 6, 10, 14, 21, 28, 35, and 42. In un-injured animals, vibrissae stimulation elicits a placing response. This response was observed when the animal placed its forelimb on the surface after vibrissae contact. The rats received 10 trials for each forelimb per test day.

Bilateral tactile adhesive removal test

This test was used in order to examine sensorimotor deficits following injury [24, 25]. The rats were removed from their cages and gently held while a small adhesive patch (121.5 mm2) was applied to the radial aspect of each forelimb. The order of attachment varied between trials. The rat was then returned to its cage and the order and latency of removal was recorded. Each rat received two trials per test day and was tested on post-operative days 2, 4, 6, 10, 14, 21, and 28. The trial ended when the rat removed both stimuli or at the end of two minutes.

Cognitive assessment

The Morris water maze was used to assess cognitive functioning [25]. A blue fiberglass tank, 1.5 m in diameter and 76 cm deep, was filled with water to a depth of 32 cm. A 10 cm2 Plexiglas platform was submerged 1.0 cm below the surface of the water. A San Diego Instruments video recording system with SMART tracking software was used to track and record the movement of each rat as it traveled over the dark background. Starting positions were randomly selected in the pool for the reference memory task. Trials measuring reference memory began on post-operative day 11 and continued for 4 days. The submerged platform was always located in the center of quadrant 2, halfway between the wall and the center of the tank. Rats were placed into the water at one of four randomly chosen starting points. Rats completed 4 trials on each test day, being released at each of the starting points. All trials ended when the rat reached the platform or after 90 seconds had elapsed. If the rat did not reach the platform within 90 seconds, it was guided to the platform and remained there for 10 seconds. Swim latency was recorded for each trial.

Histology

At 45 days post-injury, rats were anesthetized with Nembutal, (100 mg/kg, i.p.) and transcardially perfused with 0.9% phosphate buffered saline, followed by 4% paraformaldehyde. The brains were carefully extracted from the cranium, post-fixed in 4% paraformaldehyde and then cryopreserved in 30% sucrose for 3 days prior to sectioning. The brain was sectioned frozen on a sliding microtome through the extent of the injury cavity. Coronal slices (40 μm thick) were collected in a cryopreservative solution for storage. The extent of the lesion was analyzed with an Olympus microscope (BX-51) and an Olympus 13.5 megapixel digital camera (DP-70). Images of the sections throughout the extent of the injury coordinates were captured using the digital capturing system and area measures of the lesioned tissue were determined using ImageTool software. The Calvalieri method was used to calculate the volumes of the ipsilateral cortex and the contralateral cortex [26]. The number of sections and the section thickness (40 μm) were multiplied by the mean area of the lesion cavity (calculated at five stereotaxic coordinates surrounding the lesion: 2.20, 1.20, 0.20, -1.20, -2.20 relative to bregma) [27]. The extent of cortical injury was measured by calculating the percent reduction in the ipsilateral cortex compared to the contralateral cortex using the formula (1-(ipsi/contra) x 100) [24].

Statistical Analysis

Statistical evaluations were performed with SPSS v15.0 to determine if the Mg2+ dietary condition modulated behavioral recovery following injury. Data was analyzed for each behavioral test using analysis of variance (ANOVA) tests following procedures for general linear models with options for repeated measures when appropriate. Huyn-Feldt (HFP) probabilities were used when assessing the repeated measures factor. Post-hoc analyses were performed with Tukey’s HSD tests.

Results

Initial behavioral analyses indicated that there were no significant differences in performance between the animals that received sham procedures and any of the dietary manipulations. Analysis of forelimb placing data with a repeated measures ANOVA of the sham-Mg2+-normal (n = 4) sham-Mg2+-enriched (n = 5) and sham-Mg2+-deficient (n = 4) revealed no significant differences for group [F(2,10) = 0.61, p > 0.56], day [F(1.37,13.69) = 0.78, p > 0.43], or the group x day interaction [F(2.74,13.69) = 0.77, p > 0.52]. The same was also true for the tactile removal data. The effects for group [F(2,10) = 0.03, p > 0.97] and the group x day interaction [F(6.48,832.38) = 0.62, p > 0.72] were non-significant; however, the effect of day was significant [F(3.24,32.38) = 0.64, p < 0.001]. Comparison of swim latencies on the acquisition of reference memory revealed no significant differences for group [F(2,10) = 1.29, p > 0.32] and the group x day interaction [F(5.45,27.26) = 0.64, p > 0.68] were not significant; however, the effect of day was significant day [F(2.73,27.26) = 24.59, p < 0.001]. Thus, the groups were combined to create a single sham-control group. Thus, all subsequent analyses were conducted with the following groups: Mg2+-enriched (n = 9), Mg2+-deficient (n = 9), Mg2+-normal (n = 9), and sham (n = 13).

Serum Mg2+ analysis

Serum Mg2+ analysis was analyzed in a one-way ANOVA including group (Mg2+-normal, Mg2+-enriched, Mg2+-deficient) prior to injury. Two weeks of dietary manipulation of Mg2+ showed a diet-dependent change in serum levels; the main effect for serum Mg2+ was statistically significant, [F(2,27) = 31.05, p < 0.001] (figure 1). Post-hoc comparisons with Tukey’s HSD tests were conducted to determine significant differences within the group factor. Comparison of the Mg2+-normal and Mg2+-enriched diets showed a significant elevation in Mg2+ levels in the enriched group 14 [HSD (16) = 1.10, p < 0.001]. Mg2+-deficient diet showed a significant decrease in Mg2+ level compared to the Mg2+-normal diet [HSD (16) = 1.08, p < 0.001]. Thus, pre-surgical dietary manipulation of Mg2+ resulted in significant alterations of Mg2+ level prior to injury.

Vibrissae-forelimb placing test

The percentage of unsuccessful placing attempts was analyzed in a repeated measures ANOVA including group (Mg2+-normal, Mg2+-enriched, Mg2+-deficient, or Sham) and post-injury test session as the repeated measure. Following injury, the rats became more efficient in placing their contralateral forelimbs on successive trials; the main effect for day was statistically significant, [F(3.21,115.81) = 34.52, p < 0.001]. Unilateral contusions produced significant impairments in forelimb placing; the main effect of group was statistically significant, [F(3,36) = 78.74, p < 0.001] (figure 2). There was a significant difference in the rate of recovery; the group x day interaction was significant, [F(9.65,115.81) = 7.50, p < 0.001]. Post-hoc comparisons were conducted to determine differences within the group factor. Comparison of the Mg2+-normal and Mg2+-enriched diets showed no significant differences in performance on any test day. The Mg2+-deficient diet showed worse behavioral outcome compared to the Mg2+-normal diet on days 14 [HSD (16) = 28.89, p < 0.01], 21 [HSD (16) = 42.22, p < 0.02], 28 [HSD (16) = 67.78, p < 0.001], 35 [HSD (16) = 66.67, p < 0.001] and 42 [HSD (16) = 66.67, p < 0.001].

Bilateral tactile adhesive removal test

The latencies to remove the tactile stimuli were analyzed in a repeated measures ANOVA, including group (Mg2+-normal, Mg2+-enriched, Mg2+-deficient, or Sham) and post-injury test session as the repeated measure. Following injury, the rats became more efficient in removing the contralateral stimuli on their forelimbs on successive trials; the main effect for day was statistically significant, [F(2.94,105.99) = 57.28, p < 0.001]. Unilateral contusions produced significant impairments in stimuli removal; the main effect of group was statistically significant, [F(3,36) = 11.50, p <0.001] (figure 3). There was a significant difference in the rate of recovery; the group x day interaction was significant, [F(8.83,105.99) = 2.33, p < 0.02]. Post-hoc comparisons were conducted to determine differences within the group factor. Comparison of the Mg2+-normal and Mg2+-enriched diets showed no significant differences in performance on any test day (p > 0.05). The Mg2+-deficient diet showed worse behavioral outcome compared to the Mg2+-normal diet on days 6 [HSD (16) = 27.72, p < 0.05], 10 [HSD (16) = 39.11, p < 0.007], 14 [HSD (16) = 45.61, p < 0.01], and 21 [HSD (16) = 33.33, p < 0.04].

Reference memory

The swim latencies to find the hidden platform in the MWM was analyzed in a repeated measures ANOVA including group (Mg2+-normal, Mg2+-enriched, Mg2+-deficient, or Sham) and post-injury test session as the repeated measure. Following injury, the rats became more efficient at finding the platform on successive days; the main effect for day was statistically significant, [F(3.00,108.00) = 34.46, p < 0.001]. Unilateral contusions produced significant impairments in overall performance; the main effect of group was statistically significant, [F(3,36) = 5.14, p < 0.005] (figure 4). However, there was not a significant difference in the rate of recovery; the group x day interaction was not significant, [F(9.00,108.00) = 0.60, p > 0.80]. Post-hoc comparisons demonstrated that the performance on the task between the sham group and the Mg2+-normal group was not significant on any of the 4 test days (p > 0.05). This was also the case between the Mg2+-normal group and either the Mg2+-enriched, or -deficient groups (p > 0.05). The Mg2+-deficient diet showed worse behavioral outcome compared to the sham group on days 11 [HSD (18) = 15.74, p < 0.009] and 14 [HSD (18) = 22.75, p < 0.008]; whereas, the Mg2+-enriched group was significant different from the sham group on days 11 [HSD (18) = 20.71, p < 0.001], 13 [HSD (18) = 19.97, p < 0.03], and 14 [HSD (18) = 22.23, p < 0.009].

Lesion analysis

The percent reduction of the injured cortex compared to the non-injured cortex was analyzed in a one-way ANOVA including group (Mg2+-normal, Mg2+-enriched, Mg2+-deficient, or Sham) as the factor in the analysis. There were significant differences in lesion size between groups, the analysis of remaining tissue surrounding the lesion cavity was significant, [F(3,39) = 21.43, p > 0.001] (figure 5). Post-hoc comparisons with Tukey’s LSD test were conducted to determine significant differences within the group factor. Comparison of the Mg2+-normal and Mg2+-deficient diets showed a significant increase in lesion severity in the deficient group [HSD (16) = 10.06, p < 0.01]. There was a strong trend toward a reduction in lesion severity in the Mg2+-enriched group compared to the Mg2+-normal group [HSD (16) = 6.47, p > 0.09].

Discussion

The purpose of the present study was to examine the effect of dietary Mg2+ manipulations on recovery of function. After 2 weeks of diet manipulation a serum analysis was conducted at the time of cortical injury and showed that the experimental diets significantly modulated the level of circulating serum Mg2+. A strong diet-dependent effect was observed. Rats fed the Mg2+-normal diet were found to have on average 2.0 mEq/L of serum Mg2+; whereas, the Mg2+-deficient group had 0.9 mEq/L and the Mg2+-enriched had 3.1 mEq/L of serum Mg2+. Thus, the diet manipulations significantly altered serum Mg2+ levels and allowed us to determine if these dietary manipulations had any effect on recovery of function following cortical injuries.

It was found that manipulation of dietary Mg2+ did have significant effects on recovery of function. Rats fed a 2 week diet deficient in Mg2+ were significantly worse on the bilateral tactile adhesive removal and vibrissae-forelimb placing tests compared to injured rats feed a standard laboratory diet. The recovery curve of the Mg2+-deficient group showed that very little recovery of function occurred following the cortical lesions. In fact, on day 42 the average degree of impairment in this group was still at 80%, compared to 10% in the Mg2+-normal diet. Likewise, the recovery curve for the Mg2+-deficient group on the bilateral tactile removal test also showed severe impairments up to 28 days following cortical injury. Interestingly, during the assessment of reference memory performance it was found that the Mg2+-deficient diet was significantly worse compared to the non-injured, sham group, comparatively, the Mg2+-normal group was not significantly different than the sham group. Thus, the Mg2+ deficient diet produced a significant injury deficit in the MWM when there was no deficit in the injured Mg2+-normal group. Thus, the Mg2+-deficient diet worsened recovery of function on both the sensorimotor tests and on the acquisition of a reference memory task in the MWM.

In the present study, a Mg2+-enriched diet was also used to examine the effect of dietary supplementation on recovery of function. It was found on both the vibrissae-forelimb placing and bilateral tactile adhesive removal tests that Mg2+ enrichment significantly improved recovery of function compared to the Mg2+-deficient group. However, there were no statistical differences between the Mg2+-enriched and Mg2+-normal groups. This was unexpected, especially given the high serum levels of Mg2+ in the enriched group. It is possible that the levels of Mg2+ were not high enough to facilitate the recovery of function seen with these behaviors following systemic post-injury administrations [5, 28-30]. Given that serum levels of Mg2+ do not correlate well with brain tissue levels, this may also have contributed to the diminished effect in the Mg2+-enriched diet. It may also be the case that the pre-injury enriched diet might not offset the injury-induced Mg2+ decline and subsequent behavioral impairments to the same degree as post-injury systemic administrations [28-30]. The Mg2+-enriched diet appears to have impaired performance in the reference memory task to about the same extent as in the Mg2+-deficient group. At first this seems paradoxical; however, we have recently shown that daily administration of MgCl2 impaired the acquisition of reference memory in the MWM [29]. In that study, un-injured rats were given daily injections of 1 or 2 mmol/kg of MgCl2 30 minutes prior to their running in the MWM [29]. The timing of these administrations contrasts drastically to the present study, diet enrichment was discontinued at the time of injury (11 days prior to MWM testing) and the rats were placed back on the standard laboratory diet, compared to daily systemic injections prior to the MWM. Unfortunately, we do not have a serum analysis for Mg2+ at this time point; however, at the time of injury the levels were extremely high in the enriched diet group, it then must be inferred that the Mg2+ levels were high enough to interfere with maze learning. This data suggests that caution is needed with Mg2+ supplementation and learning/cognitive based tests. However, this effect only occurred in the injured animals, there were no significant impairments in learning in the Mg2+-enriched sham group.

The histological analysis revealed a diet-dependent effect on the percent reduction in the injured cortex, compared to the un-injured, contralateral cortex. The Mg2+-deficient diet showed a significantly increased reduction in the injured cortex (29.5%) compared to the contralateral cortex. This group showed the greatest extent of injury compared to all other injured groups. The Mg2+-normal group had a 21% reduction in cortical volume. The Mg2+-enriched group had the smallest lesions with a 13% reduction in cortical volume. Thus, not only do Mg2+ diet manipulations modulate recovery of function following cortical injuries but they also differentially affect lesion size.

The results of the Mg2+-deficient diet from the present study are in agreement with those reported by McIntosh and colleagues [5]. The neuroscore is a battery of 5 different tests that measure various reflexive motor and balance tasks and was shown to be significantly impaired in the Mg2+-deficient rats following FPI [5]. In the present study, we found that following CCI the deficient diet significantly impaired recovery of function on 2 different sensorimotor tests and on the acquisition of a reference memory task in the MWM. The biggest difference between these 2 studies is in post-injury mortality. Following FPI, a 53% mortality was observed; whereas, following CCI we found no mortality. Given the differences between FPI and CCI (FPI usually shows greater mortality compared to CCI), this result is not surprising.

Conclusion

The results of this study have demonstrated that manipulating dietary Mg2+ levels prior to injury had dramatic effects on recovery of function and extent of injury. A Mg2+-deficient diet significantly reduced the serum levels of Mg2+ and significantly exacerbated sensorimotor and cognitive deficits following cortical injuries. The Mg2+-enriched diet increased the serum level of Mg2+ prior to injury but did not significantly improve sensorimotor performance compared to the Mg2+-control diet; however, cognitive performance in the MWM was impaired. In general, the results of this study suggest that dietary status (especially concerning Mg2+) is an important factor in recovery of function following injury and warrants more experimental consideration.

Acknowledgments

This research supported by grant from the University of North Carolina Institute of Nutrition.

References

1 Garfinkel L, Garfinkel D. Magnesium regulation of glycolytic pathway and the enzymes involved. Magnesium 1985; 4: 60-72.

2 Bara M, Guiet-Bara A. Potassium, magnesium and membranes. Magnesium 1984; 3: 212-25.

3 Rubin H. Magnesium deprivation reproduces the co-ordinate effects of serum removal or cortisol addition on transport and metabolism in chick embryo fibroblasts. J Cell Physiol 1976; 89: 613-26.

4 Aikawa JK. In: Magnesium: it’s biological significance. Boca Raton: CRC, 1981: 21-9.

5 McIntosh TK, Faden AI, Yamakami I, Vink R. Magnesium deficiency exacerbates and pretreatment improves outcome following traumatic brain injury in rats: 31P magnetic resonance spectroscopy and behavioral studies. J Neurotrauma 1988; 5: 17-31.

6 Vink R, McIntosh TK, Demediuk P, Faden AI. Decrease in total and free magnesium concentration following traumatic brain injury in rats. Biochem Biophys Res Commun 1987; 149: 594-9.

7 Vink R, McIntosh TK, Demediuk P, Weiner MW, Faden AI. Decline in intracellular free Mg2+ is associated with irreversible tissue injury after brain trauma. J Biol Chem 1988; 263: 757-61.

8 Vink R, McIntosh TK. Pharmacological and physiological effects of magnesium on experimental traumatic brain injury. Magnes Res 1990; 3: 163-9.

9 Heath DL, Vink R. Traumatic brain axonal injury produces sustained decline in intracellular free magnesium concentration. Brain Res 1996; 738: 150-3.

10 Hoane MR, Barth TM. The window of opportunity for administration of magnesium therapy following focal brain injury is 24 hours but task dependent in the rat. Physiol Behav 2002; 76: 271-80.

11 Hoane MR, Barbay S, Barth TM. Large cortical lesions produce enduring forelimb placing deficits in un-treated rats and treatment with NMDA antagonists or anti-oxidant drugs induces behavioral recovery. Brain Res Bull 2000; 53: 175-86.

12 Hoane MR, Raad C, Barth TM. Non-competitive NMDA antagonists and anti-oxidant drugs reduce striatal atrophy and facilitate recovery of function following lesions of the rat cortex. Restor Neurol Neurosci 1997; 11: 71-82.

13 Hoane MR, Irish SL, Marks BB, Barth TM. Preoperative regimens of magnesium facilitate recovery of function and prevent subcortical atrophy following lesions of the rat sensorimotor cortex. Brain Res Bull 1998; 45: 45-51.

14 Bareyre FM, Saatman KE, Raghupathi R, McIntosh TK. Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats. J Neurotrauma 2000; 17: 1029-39.

15 McIntosh TK, Vink R, Yamakami I, Faden AI. Magnesium protects against neurological deficit after brain injury. Brain Res 1989; 482: 252-60.

16 McIntosh TK, Vink R, Soares H, Hayes R, Simon R. Effect of noncompetitive blockage of N-methyl-D-aspartate receptors on the neurochemical sequelae of experimental brain injury. J Neurochem 1990; 55: 1170-9.

17 Guluma KZ, Saatman KE, Brown AL, Raghupathi R, McIntosh TK. Sequential pharmacotherapy with magnesium chloride and basic fibroblast growth factor after fluid percussion brain injury results in less neuromotor efficacy than that achieved with magnesium alone. J Neurotrauma 1999; 16: 311-21.

18 Heath DL, Vink R. Improved motor outcome in response to magnesium therapy received up to 24 hours after traumatic diffuse axonal brain injury in rats. J Neurosurg 1999; 90: 504-9.

19 Heath DL, Vink R. Optimization of magnesium therapy after severe diffuse axonal brain injury in rats. J Pharmacol Exp Ther 1999; 288: 1311-6.

20 Altura BM, Gebrewold A, Zhang A, Altura BT, Gupta RK. Magnesium deficiency exacerbates brain injury and stroke mortality induced by alcohol: a 31P-NMR in vivo study. Alcohol 1998; 15: 181-3.

21 Bardgett ME, Schultheis PJ, McGill DL, Richmond RE, Wagge JR. Magnesium deficiency impairs fear conditioning in mice. Brain Res 2005; 1038: 100-6.

22 Bardgett ME, Schultheis PJ, Muzny A, Riddle MD, Wagge JR. Magnesium deficiency reduces fear-induced conditional lick suppression in mice. Magnes Res 2007; 20: 58-65.

23 Barbre AB, Hoane MR. Magnesium and riboflavin combination therapy following cortical contusion injury in the rat. Brain Res Bull 2006; 69: 639-46.

24 Hoane MR, Tan AA, Pierce JL, Anderson GD, Smith DC. Nicotinamide treatment reduces behavioral impairments and provides cortical protection after fluid percussion injury in the rat. J Neurotrauma 2006; 23: 1535-1548.

25 Hoane MR, Akstulewicz SL, Toppen J. Treatment with vitamin B3 improves functional recovery and reduces GFAP expression following traumatic brain injury in the rat. J Neurotrauma 2003; 20: 1189-98.

26 Coggeshall RE. A consideration of neural counting methods. Trends Neurosci 1992; 15: 9-13.

27 Paxinos G, Watson C. The rat brain in stereotaxic coordinates. New York: Elsevier, 2005.

28 Hoane MR. Treatment with magnesium improves reference memory but not working memory while reducing GFAP expression following traumatic brain injury. Restor Neurol Neurosci 2005; 23: 67-77.

29 Hoane MR. Assessment of cognitive function following magnesium therapy in the traumatically injured brain. Magnes Res 2007; 20: 229-36.

30 Hoane MR, Barth TM. The behavioral and anatomical effects of MgCl2 therapy in an electrolytic lesion model of cortical injury in the rat. Magnes Res 2001; 14: 51-63.


 

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