Autoradiographic localization of N-type VGCCs in gerbil hippocampus and failure of omega-conotoxin MVIIA to attenuate neuronal injury after transient cerebral ischemia.
Brain Res
; 907(1-2): 61-70, 2001 Jul 13.
Article
em En
| MEDLINE
| ID: mdl-11430886
ABSTRACT
In the mammalian central nervous system, transient global ischemia of specific duration causes selective degeneration of CA1 pyramidal neurons in hippocampus. Many of the ischemia-induced pathophysiologic cascades that destroy the neurons are triggered by pre- and postsynaptic calcium entry. Consistent with this, many calcium channel blockers have been shown to be neuroprotective in global models of ischemia. omega-Conotoxin MVIIA, a selective N-type VGCC blocker isolated from the venom of Conus magus, protects CA1 neurons in the rat model of global ischemia, albeit transiently. The mechanism by which this peptide renders neuroprotection is unknown. We performed high-resolution receptor autoradiography with the radiolabeled peptide and observed highest binding in stratum lucidum of CA3 subfield, known to contain inhibitory neurons potentially important in the pathogenesis of delayed neuronal death. This finding suggested that the survival of stratum lucidum inhibitory neurons might be the primary event, leading to CA1 neuroprotection after ischemia. Testing of this hypothesis required the reproduction of its neuroprotective effects in the gerbil model of global ischemia. Surprisingly, we found that omega-MVIIA did not attenuate CA1 hippocampal injury after 5 min of cerebral ischemia in gerbil. Possible reasons are discussed. Lastly, we show that the peptide can be used as a synaptic marker in assessing short and long-term changes that occur in hippocampus after ischemic injury.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bloqueadores dos Canais de Cálcio
/
Ataque Isquêmico Transitório
/
Fármacos Neuroprotetores
/
Canais de Cálcio Tipo N
/
ômega-Conotoxinas
/
ômega-Conotoxina GVIA
/
Hipocampo
/
Proteínas do Tecido Nervoso
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Brain Res
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos