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Recovery of function in cytoprotected cerebral cortex in rat stroke model assessed by functional MRI
Andre Sauter1, Torsten Reese, Robert Pórszász
1Nervous System, Novartis Pharma AG, Basel, Switzerland.
Abstract:
Functional recovery in cytoprotected somatosensory cortex in a rat stroke model was studied using functional MRI (fMRI). Calcium antagonist treatment (isradipine) following permanent middle cerebral artery occlusion (pMCAO) reduced the infarct volume by 33 +/- 9%. The somatosensory cortex representing the forepaws was spared from infarction; however, cerebral blood flow (CBF) was significantly reduced in this area 24 hr following pMCAO. Neural function was assessed at days 1, 2, 5, and 12 following pMCAO by fMRI using electrical stimulation of both forepaws. Vehicle-treated rats did not show fMRI responses in the infarcted somatosensory cortex throughout the study. Several of the isradipine-treated animals displayed functional recovery in the cytoprotected cortex at days 5 (3/5 rats) and 12 (5/10). Correlations with fMRI signals showed that normal T2 and ADC values in the respective brain areas are necessary, but not sufficient prerequisites for functionality. Recovery of neural function is associated with normalization of CBF in the cytoprotected brain area.
Insights
Isradipine treatment in a rat stroke model reduced infarct size and promoted functional recovery in the somatosensory cortex. This recovery correlated with normalized cerebral blood flow (CBF) in the affected brain area.
Area of Science:
- Neuroscience
- Stroke Research
- Neuroimaging
Background:
- Stroke, particularly middle cerebral artery occlusion (MCAO), leads to significant neuronal damage and functional deficits.
- Cytoprotective agents are explored to mitigate stroke-induced brain injury.
- Functional magnetic resonance imaging (fMRI) is a key tool for assessing brain function and recovery.
Purpose of the Study:
- To investigate the effects of the calcium antagonist isradipine on functional recovery in the cytoprotected somatosensory cortex following permanent middle cerebral artery occlusion (pMCAO) in a rat model.
- To assess the relationship between cerebral blood flow (CBF), brain tissue characteristics, and neural function recovery using fMRI.
- To determine if isradipine treatment facilitates functional recovery in the spared, yet hemodynamically compromised, somatosensory cortex.
Main Methods:
- A rat model of permanent middle cerebral artery occlusion (pMCAO) was established.
- Rats received either isradipine (calcium antagonist) or vehicle treatment post-MCAO.
- fMRI was employed to assess neural function via electrical forepaw stimulation at multiple time points (days 1, 2, 5, 12) post-stroke.
- Infarct volume, T2, and apparent diffusion coefficient (ADC) values were measured.
- Cerebral blood flow (CBF) changes were monitored in the somatosensory cortex.
Main Results:
- Isradipine treatment reduced infarct volume by 33 +/- 9%.
- Despite spared tissue, the somatosensory cortex showed significantly reduced CBF 24 hours post-pMCAO.
- Vehicle-treated rats showed no fMRI responses in the infarcted cortex.
- Isradipine-treated rats exhibited functional recovery in the cytoprotected cortex at days 5 (3/5) and 12 (5/10).
- Normal T2 and ADC values were necessary but not sufficient for functional recovery.
- Neural function recovery was associated with CBF normalization in the cytoprotected area.
Conclusions:
- Isradipine treatment offers neuroprotection and promotes functional recovery in a rat stroke model.
- Restoration of cerebral blood flow is crucial for the recovery of neural function in the cytoprotected brain regions post-stroke.
- fMRI is a valuable tool for monitoring functional recovery and its underlying physiological changes after stroke intervention.