Early Synaptic Composition Changes after Global Cerebral Ischemia (P05.225)

OBJECTIVE: We investigated the activity of the synaptic protein calcium/calmodulin kinase II (CaMKII) in response to hypoxia induced stress. BACKGROUND: Neurological impairment from oxygen deprivation after cardiac arrest (CA) hinders synaptic transmission and cellular action potential firing of the neurons in the brain. DESIGN/METHODS: Thirteen male adult Wistar rats underwent 7-minute asphyxial CA, with 2 additional rats as shams. Multiunit activity (MUA) was continuously recorded from the primary somatosensory forelimb area during baseline, injury, and early recovery. We characterized the recovery of electrophysiological signals by analyzing the neural firing rate and short-latency responses of evoked neural activities. After CA, the animals were euthanized (1) 5 minutes after resuscitation (Pre-spike Group, n=3), (2) immediately after early recovery of spontaneous multiunit spike (Early Group, n=5), or (3) upon later recovery of multiunit spike when SSEP N10 amplitude recovered to 50% of its baseline or 60 minutes after resuscitation (Late Group, n=5). Total and activated CaMKII in the synaptosomal fractions of brains were quantified using Western Blot analysis. RESULTS: The Late Group had significant MUA firing rate (37.6 ±12.9%) normalized to baseline, compared to the Early Group (2.0±1.7%, p=0.01) and the Pre-spike Group (0.2±0.1%, p=0.01). An increase in total CaMKII was found in synaptosomal fractions of the Pre-spike Group, compared to shams (p=0.003) and the Late Group (p=0.014). A strong activation of CaMKII was found in the Pre-spike Group (p=0.011) compared to the Late group, with no significant difference between the Early Group and the Late Group. CONCLUSIONS: Early CaMKII change is associated with early burst recovery of neuron spike activity after global cerebral ischemia. Activation of CaMKII may be associated with the recovery of synaptic protein regulation and responsible for or coincident with recovery of neural spike activity. Further studies may elucidate the mechanistic link between synaptic proteins, synaptic strength recovery, and restoration of electrical brain function. Supported by: American Heart Association #09SDG2110140 (to XJ) and NIH RO1HL071568 (to NVT). Disclosure: Dr. Jia has nothing to disclose. Dr. Buitrago Blanco has nothing to disclose. Dr. Sharma has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Payton has nothing to disclose. Dr. Nitish Thakor recieved personal compensation from Infinite Biomedical Technologies, LLC for consulting services....Dr. Nitish Thakor holds equity interest in Infinite Biomedical Technologies, LLC. Dr. Thakor has received personal compensation for activities with Infinite Biomedical Technologies, LLC as a consultant. Dr. Thakor holds stock and/or stock options in Infinite Biomedical Technologies, LLC, which sponsored research in which Dr. Thakor was involved as an investigator. Dr. Huganir has received personal compensation for activities with Millipore Corporation as a consultant. Dr. Huganir has received royalty payments from Millipore Corporation. Dr. Geocadin has nothing to disclose.