Magnesium chloride alone or in combination with diazepam fails to prevent hippocampal damage following transient forebrain ischemia.
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.
Milani
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H
Departamento de Farmácia e Farmacologia, Centro de Ciências da Saúde, Universidade Estadual de Maringá, Maringá, PR, Brasil. milani@dff.uem.br
Lepri
E R
ER
Giordani
F
F
Favero-Filho
L A
LA
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology; D003975:Diazepam / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006624:Hippocampus / Q000098:blood supply*; D015636:Magnesium Chloride / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016548:Prosencephalon / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar
D018696:Neuroprotective Agents; D015636:Magnesium Chloride; D003975:Diazepam