Abstract
In the central nervous system, magnesium ion (Mg2+) acts as an endogenous modulator of N-methyl-D-aspartate (NMDA)-coupled calcium channels, and may play a major role in the pathomechanisms of ischemic brain damage. In the present study, we investigated the effects of magnesium chloride (MgCl2, 2.5, 5.0 or 7.5 mmol/kg), either alone or in combination with diazepam (DZ), on ischemia-induced hippocampal cell death. Male Wistar rats (250-300 g) were subjected to transient forebrain ischemia for 15 min using the 4-vessel occlusion model. MgCl2 was applied systemically (sc) in single (1x, 2 h post-ischemia) or multiple doses (4x, 1, 2, 24 and 48 h post-ischemia). DZ was always given twice, at 1 and 2 h post-ischemia. Thus, ischemia-subjected rats were assigned to one of the following treatments: vehicle (0.1 ml/kg, N = 34), DZ (10 mg/kg, N = 24), MgCl2 (2.5 mmol/kg, N = 10), MgCl2 (5.0 mmol/kg, N = 17), MgCl2 (7.5 mmol/kg, N = 9) or MgCl2 (5 mmol/kg) + DZ (10 mg/kg, N = 14). Seven days after ischemia the brains were analyzed histologically. Fifteen minutes of ischemia caused massive pyramidal cell loss in the subiculum (90.3%) and CA1 (88.4%) sectors of the hippocampus (P<0.0001, vehicle vs sham). Compared to the vehicle-treated group, all pharmacological treatments failed to attenuate the ischemia-induced death of both subiculum (lesion: 86. 7-93.4%) and CA1 (lesion: 85.5-91.2%) pyramidal cells (P>0.05). Both DZ alone and DZ + MgCl2 reduced rectal temperature significantly (P<0.05). No animal death was observed after drug treatment. These data indicate that exogenous magnesium, when administered systemically post-ischemia even in different multiple dose schedules, alone or with diazepam, is not useful against the histopathological effects of transient global cerebral ischemia in rats.
Highlights
Transient global cerebral ischemia results in hippocampal cell death both in animal models [1,2] and in humans, for example, victims of reversible cardiac arrest [3]
We investigated the effects of magnesium chloride (MgCl2, 2.5, 5.0 or 7.5 mmol/kg), either alone or in combination with diazepam (DZ), on ischemiainduced hippocampal cell death
The present study demonstrates that the systemic application of increasing doses of MgCl2 employing either a single or multiple administration schedule does not provide neuroprotection against delayed hippocampal cell death induced by transient forebrain ischemia in the adult rat
Summary
Transient global cerebral ischemia results in hippocampal cell death both in animal models [1,2] and in humans, for example, victims of reversible cardiac arrest [3]. Increased intracellular calcium seems to play an important role in the pathophysiology of delayed neuronal death caused by cerebral ischemia. There is evidence of a relationship between the reduction or loss of the Mg2+ blockade of the NMDA response and persistent, neuronal hyperexcitability, which evolves to structural changes in the dendrites and to hippocampal cell death [8]. Such neuronal overactivation may be related to the cause rather than the effect of ischemia-induced neurodegeneration since it can be detected long before cell loss [9]. The role of endogenous Mg2+ in modulating calcium influx through the NMDA glutamate receptor makes it a candidate for neuroprotective therapy
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Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
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