Acute Cytoskeletal Alterations and Cell Death Induced by Experimental Brain Injury Are Attenuated by Magnesium Treatment and Exacerbated by Magnesium Deficiency

• Published in: Journal of neuropathology and experimental neurology Vol. 60; no. 2; pp. 183 - 194
• Main Authors: SAATMAN, KATHRYN E, BAREYRE, FLORENCE M, GRADY, M SEAN, MCINTOSH, TRACY K
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.02.2001; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain Injuries - drug therapy; Brain Injuries - metabolism; Brain Injuries - pathology; Calpain - drug effects; Calpain - metabolism; Cell Death - drug effects; Cell Death - physiology; Cell Survival - drug effects; Cell Survival - physiology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Cytoskeleton - pathology; Disease Models, Animal; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Injuries of the nervous system and the skull. Diseases due to physical agents; Magnesium - metabolism; Magnesium - pharmacology; Magnesium Deficiency - complications; Magnesium Deficiency - pathology; Magnesium Deficiency - physiopathology; Male; Medical sciences; Microtubule-Associated Proteins - drug effects; Microtubule-Associated Proteins - metabolism; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Spectrin - drug effects; Spectrin - metabolism; Traumas. Diseases due to physical agents; Immunohistochemistry; Nervous system diseases; Pathophysiology; Rat; Craniocerebral; Rodentia; Diseases of the osteoarticular system; Trauma; Cerebral disorder; Pathology; Vertebrata; Experimental disease; Mammalia; Animal; Central nervous system disease; Skull disease; Cytoskeleton; Magnesium
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1093/jnen/60.2.183

Traumatic brain injury results in a profound decline in intracellular magnesium ion levels that may jeopardize critical cellular functions. We examined the consequences of preinjury magnesium deficiency and post-traumatic magnesium treatment on injury-induced cytoskeletal damage and cell death at 24 h after injury. Adult male rats were fed either a normal (n = 24) or magnesium-deficient diet (n = 16) for 2 wk prior to anesthesia and lateral fluid percussion brain injury (n = 31) or sham injury (n = 9). Normally fed animals were then randomized to receive magnesium chloride (125 μmol, i.v., n = 10) or vehicle solution (n = 11) at 10 min postinjury. Magnesium treatment reduced cortical cell loss (p < 0.05), cortical alterations in microtubule-associated protein-2 (MAP-2) (p < 0.05), and both cortical and hippocampal calpain-mediated spectrin breakdown (p < 0.05 for each region) when compared to vehicle treatment. Conversely, magnesium deficiency prior to brain injury led to a greater area of cortical cell loss (p < 0.05 compared to vehicle treatment). Moreover, brain injury to magnesium-deficient rats resulted in cytoskeletal alterations within the cortex and hippocampus that were not observed in vehicle- or magnesium-treated animals. These data suggest that cortical cell death and cytoskeletal disruptions in cortical and hippocampal neurons may be sensitive to magnesium status after experimental brain injury, and may be mediated in part through modulation of calpains.