Correlation of neuronal cell death, functional image and electrical activity after a focal cerebral ischemia in the mouse
Functional loss and recovery are critical issues after an ischemic insult. The focal ischemia in the cerebral barrel cortex is an ideal model for studying short- and long-term functional alterations of sensory cortex. We extend the “mini-stroke” model from rat to mouse by studying the correlation between neuronal injury and functional activities, intrinsic optical signals (IOS) and evoked potentials in response to whisker stimulation in the ischemic barrel cortex of the mouse. Methods. Adult mice were anesthetized and multiple branches of the middle cerebral artery (MCA) that supply the right side of the barrel cortex were permanently ligated. IOS were used for identifying the barrel cortex; a recording electrode was placed in multiple sites of the barrel cortex in and around the ischemic region. Local cerebral blood flow (LCBF) was measured by Laser Doppler and quantitative autoradiography. Cell injury was determined by immunohistochemistry after the ischemia. Results. Immediately after MCA ligations LCBF was markedly reduced to 10% of control levels followed by simultaneous losses of IOS and evoked potentials in the ischemic side of the cortex. IOS responses and evoked potential were closely matched in all cases. TUNEL positive and/or CM-1 positive cell death and lack of cytochrome oxidase staining in the ischemic core were found 2 days after ischemia and continued for up to 10 days later. With the exception of ischemic injury, IOS image and evoked potential were partially recovered 30 days after the ischemia. Conclusion. The small focal stroke in the mouse barrel cortex shows high reliability for functional assays and their correlation to LCBF. Apoptosis may contribute to the ischemic barrel injury. The functional recovery 30 days after ischemia implies a neurovascular plasticity that is beneficial for long-term rehabilitation after a focal ischemic stroke. Supported by grants from NIH (NS37372) and AHA (IBN-9817151).