The goal of this project is to determine the changes in neural function after an intracerebral hemorrhage (ICH) is produced in the brain of the swine, which resembles the human brain in many respects, in order to infer the pathophysiology of stroke in patients with an ICH. The pathophysiology of ICH is not well understood, although it is associated with severe neurological deficits and protracted incomplete recovery. The proposed longitudinal study will provide the time course of electrophysiological, anatomical and biochemical changes in the porcine brain after producing an ICH with collagenase which slowly breaks down the blood brain barrier. The electrophysiological characteristics of the ICH core within the primary somatosensory cortex, perihernatomal and functionally related, remote regions of the brain will be monitored non-invasively with somatic evoked magnetic fields (SEFs), and scalp somatic evoked potentials (SEPs) from the time of collagenase injection to the chronic recovery period up to 28 days. The investigators will look for changes in evoked responses elicited by the snout stimulation in different areas of the somatosensory cortex and study the development of diaschisis observed in their preliminary study. Pathophysiological development of the ICH, including edema formation and volurnetric progression of the hemorrhage, and metabolic changes will be characterized using magnetic resonance imaging (MRI) and spectroscopy (MRS). Non-invasive SEF and SEP data will be compared with those recorded with epi-and intracortical electrodes to establish the physiological basis for the non-invasively measured signals. The SEF and SEP will be also compared with the degree of inflammatory activity, measured by the level of matrix metalloproteinases (MAPS) in the ICH core and functionally related areas to establish whether the neuroinflammatory response is related to abnormal non-invasively measured electrophysiological signals and how it affects neural functioning. In addition, SEF data from stroke patients will be obtained to test the predictions from the ICH animal studies that functionally connected, remote regions of the brain may be abnormal following a focal brain injury. These proposed studies should eventually serve as important bases for understanding the sequela of ICH and in interpreting magnetoencephalography (MEG), electroencephalography (EEG) and MRS signals from stroke patients.
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