NEUROPHYSIOLOGY OF HIPPOCAMPAL NEURONS AFTER ISCHEMIA

  • Xu, Zao, (PI)

Project: Research project

Description

DESCRIPTION My long term goal is to identify
mechanisms of neuronal damage following transient ischemia and provide
a basis for evaluating potential treatment for postischemic injury in
the CNS. Cerebrovascular disease (stroke) is one of the leading cause
of death in the United States. Over 500,000 patients suffer the effects
of hypoxic- ischemic' brain damage yearly. Excitotoxic effect of
excessive glutamate release during ischemia has been postulated as one
of the primary factors in postischemic neuronal damage. However,
previous studies fail to provide a consistent picture of neuronal
hyperactivity following ischemia with extracellular recording or brain
slice preparations. Using in vivo intracellular recording and staining
techniques, the objective of the proposed research is to elucidate'
changes in neuronal and synaptic activity that occur in pyramidal
neurons of rat hippocampus after transient forebrain ischemia, and to
determine their roles in selective neuronal injury following- -ischemia.
The main hypotheses to be tested are whether neuronal activity of CAl
neurons is enhanced after transient ischemia, and whether such
enhancement is due to a) enhanced synaptic transmission or b) increased
intrinsic excitability of CAl neurons. Secondarily it will be
determined whether neurophysiological changes differ in ischemia-
sensitive CAl neurons and ischemia-resistant CA3 neurons following,
ischemia, thereby identifying those factors that may contribute to the
selective vulnerability of CAl neurons. Forebrain ischemia of 5-20 min
duration will be induced using the 4-vessel occlusion method. Spontaneous
activities and evoked potentials of CAl and CA3 neurons before, during,
and at different intervals after transient ischemia will be compared to
reveal the postischemic changes of neuronal activity and synaptic
transmission. Changes in neuronal excitability will be studied by
comparing membrane properties of the neuron before and after transient
ischemia. Neurophysiological changes associated with selective neuronal
injury will be determined by comparing the postischemic responses of CA
I and CA3 neurons. The neurons in which the recordings are made will be
identified by intracellular staining with neurobiotin. The proposed
experiments will bridge the gap between previous extracellular recording
studies of ischemia in vivo and intracellular recording studies of hypoxia/
ischemia in vitro. The results of this study will improve understanding of
the mechanisms of brain damage upon resuscitation following cardiac arrest.
StatusFinished
Effective start/end date6/20/945/31/99

Funding

  • National Institutes of Health: $111,470.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Neurophysiology
Ischemia
Neurons
Prosencephalon
Synaptic Transmission
Wounds and Injuries
Cerebrovascular Disorders
Brain Hypoxia
Staining and Labeling
Heart Arrest
Evoked Potentials
Resuscitation
Glutamic Acid
Hippocampus

Keywords

  • Medicine(all)
  • Neuroscience(all)