Characterization of Plasma Magnesium Concentration and Oxidative Stress Following Graded Traumatic Brain Injury in Humans

Abstract

Plasma magnesium, calcium, and oxidative status were investigated in 31 male casualties with traumatic brain injury (TBI) during a 7-day posttraumatic period. The study group consisted of eight patients with mild closed head injury (Glasgow Coma Scale score [GCS] of 13-15), 10 patients with extensive penetrating head injury (GCS 4-6), and 13 patients with blast injuries but without direct head trauma. The latter group was included since previous experimental and clinical data have confirmed the development of indirect brain trauma in patients with blast injuries. Patients with multiple injuries were not included. Significant declines in plasma divalent cations were found in GCS 4-6 patients immediately after TBI and persisting for the entire 7-day study period. Similar changes in magnesium, but not calcium, were present in the GCS 13-15 and the blast injury groups, but only up until day 3 after injury. Alterations in lipid peroxidation products and superoxide anions were also observed following TBI. Increased lipid peroxidation was noted in all three groups over the entire posttraumatic period while increases in superoxide anion generation occurred transiently immediately following TBI. Thereafter, in the GCS 13-15 and blast injury groups, superoxide anions subsequently normalized, whereas in extensive head injury (GCS 4-6), superoxide anion generation significantly declined. A negative correlation between magnesium balance and oxidative stress was observed in all patients immediately after injury persisting in GCS 4-6 patients to the end of the observation period. Our findings suggest an interrelationship between magnesium changes and blood oxidants/antioxidants after TBI, which could be of both diagnostic and prognostic value in patients with neurotrauma.

Regulation of intracellular free magnesium in central nervous system injury

“…Significant declines in blood free magnesium concentration have been reported following both direct (97) and indirect clinical neurotrauma (98). These data show that both direct and indirect neurotrauma cause significant changes in divalent cation balance, and that following indirect neurotrauma, these changes are correlated to alterations in oxidative status/antioxidant defense.…”

Use of Magnesium in Traumatic Brain Injury

“…50 In humans with graded TBI with GCS scores of 4 -6 (extensive, penetrating injury) and 13-15 (mild, closed injury), a time-dependent increase of plasma ionized magnesium was observed for 7 days. 27 There was a persistent production of reactive oxygen species malondialdehyde and a delayed decrease of the antioxidant superoxide dismutase, suggesting increased antioxidant utilization. The study showed a correlation between the decline in plasma ionized magnesium concentration and the development of oxidative stress in TBI.…”

“…26 These findings were confirmed in TBI patients: administration of magnesium sulfate reduced oxidative stress after TBI in humans. 27 In patients with subarachnoid hemorrhage undergoing temporary cerebral artery occlusion for clipping of cerebral aneurysm, treatment with magnesium sulfate dilated the leptomeningeal arteries and enhanced collateral blood flow and tissue oxygenation. 28 Molecular mechanisms have been studied on the efficacy of magnesium in attenuating the neurological damage in TBI.…”

“…The study showed a correlation between the decline in plasma ionized magnesium concentration and the development of oxidative stress in TBI. 27 …”

Multifunctional Drugs for Head Injury

“…26 The ROS are highly reactive molecules that contain an unpaired electron in the outermost orbit, increasing their potential for chemical reactivity. 27 As normal by-products of oxidative metabolism, these ROS, or free radicals, are constantly produced, but their concentration is usually tightly controlled by endogenous antioxidant mechanisms.…”