In vivo model systems that can evaluate neuronal death, survival, and regeneration are critical to revealing basic mechanisms of neuronal response and developing strategies for CNS repair. We propose a distinct experimental model of CNS degeneration following lesions to the perforant path connecting the hippocampus and the entorhinal cortex. Within 2 weeks of a unilateral aspirative perforant p...

  Background: It is well known that the hippocampus, the CA1 Pyramidal cells in particular, is selectively vulnerable during global cerebral ischemia. Recently, it is observed that pentoxifylline has a neuroprotective effect. This study explored the pharmacological relationship between ischemia-induced cell death of the hippocampus and the efficacy of a vasodilator agent (pentoxifylline) in the...

Transient, severe forebrain or global ischemia leads to delayed cell death of pyramidal neurons in the hippocampal CA1. The precise molecular mechanisms underlying neuronal cell death after global ischemia are as yet unknown. Glutamate receptor-mediated Ca2+ influx is thought to play a critical role in this cell death. In situ hybridization revealed that the expression of mRNA encoding GluR2 (t...

Transient brain ischemia induces an inhibition of translational rates and causes delayed neuronal death in selective regions and cognitive deficits, whereas these effects do not occur in resistant areas. The translational repressor eukaryotic initiation factor (eIF) 4E-binding protein-2 (4E-BP2) specifically binds to eIF4E and is critical in the control of protein synthesis. To link neuronal de...

objective: morphological changes of ca1 neurons in rat hippocampus after transient and permanent focal cerebral ischemia were studied to clarify the nature of postischemic cell death in the subfield. materials and methods: male adult rats were divided into 3 groups: control (shamoperated), transient ischemic group (30 minutes of mcao followed by 48 hours of reperfusion), and permanent ischemic ...

An initial overload of intracellular Ca2+ plays a critical role in the delayed death of hippocampal CA1 neurons that die a few days after transient ischemia. Without direct evidence, the prevailing hypothesis has been that Ca2+ overload may recur until cell death. Here, we report the first measurements of intracellular Ca2+ in living CA1 neurons within brain slices prepared 1, 2, and 3 days aft...

The clinical manifestations of inherited neurodegenerative diseases are often delayed for periods from years to decades. This observation has led to the idea that, in these disorders, neurons die from cumulative damage. A critical prediction of the cumulative damage hypothesis is that the probability of neuronal death increases with age. However, we recently demonstrated, in 17 examples of neur...