Acute treatment with MgSO₄ attenuates long‐term hippocampal tissue loss after brain trauma in the rat

Abstract

Previous studies have shown that magnesium salts and the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, NPS 1506, attenuated short-term cognitive deficits and histopathological changes associated with traumatic brain injury (TBI). We evaluated the long-term effects of both therapies after brain trauma. Young adult rats were subjected to parasagittal fluid-percussion brain injury and received either MgSO(4) (125 micromol/400 g rat; n = 12) 15 min post-injury, NPS 1506 (1.15 mg/kg; n = 12) 15 min and 4 hr post-injury, or vehicle (n = 9) 15 min post-injury. Uninjured animals (sham) received vehicle (n = 10). Learning function in these animals was evaluated using a water maze paradigm 8 months after injury or sham treatment, and the brains were examined for cortical and hippocampal tissue loss. Compared to sham animals, injured vehicle-treated animals displayed a substantial learning dysfunction, indicated by an increased latency to find a hidden platform in the water maze (P < 0.001). No improvements in learning, however, were found for injured animals treated with NPS 1506 or MgSO(4). Injury induced >30% loss of tissue in the ipsilateral cortex in vehicle-treated animals that was not reduced in animals treated with either NPS 1506 or MgSO(4). Treatment with MgSO(4) significantly reduced progressive tissue loss in the hippocampus (P < 0.001). These findings are the first to demonstrate long-term neuroprotection of hippocampal tissue by an acute treatment in a TBI model. These data also show that the previously reported broad efficacy of MgSO(4) or NPS 1506 observed shortly after brain trauma could not be detected 8 months post-injury.

Comparing Effects of Intraventricular Hypertonic Saline and Magnesium Sulfate Application on Diffuse Brain Injury in Rats

“…However, magnesium plays an important role in the conduction of the nervous system via a voltage-gated antagonist action at the NMDA receptor. Therefore it has neuroprotective effect as shown in previous studies (19,20). Our findings confirm neuroprotective effect of magnesium sulphate in TBI model by decreasing the number of the injured cells while hypertonic saline had no direct effect on injured neural tissue.…”

Traumatic brain injury induces biphasic upregulation of ApoE and ApoJ protein in rats

“…All animals were weighed periodically and no differences were noted between injured and noninjured groups throughout 6 months of analysis. Although the injured animals seemed generally normal, we have observed previously that mild neurologic motor dysfunction and moderate cognitive deficits persist for up to 1 yr after FP injury (Leoni et al, 2000; Pierce et al, 1998; Browne et al, 2004).…”

Magnesium lithospermate B possesses inhibitory activity on Na+,K+-ATPase and neuroprotective effects against ischemic stroke

“…Furthermore, the protective effects against cerebral ischemia-reperfusion injury and attenuation of the infarction area in a middle cerebral artery occlusion animal model by a mixture of total salvianolic acids extracted from Danshen were also reported previously [29] . Recent studies indicate that Mg 2+ possesses a neuroprotective effect on brain trauma in rats [30] and is capable of modu-lating the L-type calcium channel in the myocardium [31] . Since MLB is composed of 2 portions, an organic moiety of caffeic acid tetramer and the cation Mg 2+ , it is also possible that the Mg 2+ salt-bridged against MLB may partly play a role to protect the brain against ischemic injury.…”