Chronic inflammation and apoptosis propagate in ischemic cerebellum and heart of non-human primates

// Sandra A. Acosta 1,* , Sherwin Mashkouri 1,* , Diana Nwokoye 1 , Jea Y. Lee 1 and Cesar V. Borlongan 1 1 Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, USA * These authors have contributed equally to this work Correspondence to: Cesar V. Borlongan, email: // Keywords : secondary injury, neurodegeneration, cell death, Purkinje cells, Pathology Section Received : March 14, 2017 Accepted : May 17, 2017 Published : June 01, 2017 Abstract The major pathological consequences of cerebral ischemia are characterized by neurological deficits commonly ascribed to the infarcted tissue and its surrounding region, however, brain areas, as well as peripheral organs, distal from the original injury may manifest as subtle disease sequelae that can increase the risks of co-morbidities complicating the disease symptoms. To evaluate the vulnerability of the cerebellum and the heart to secondary injuries in the late stage of transient global ischemia (TGI) model in non-human primates (NHP), brain and heart tissues were collected at six months post-TGI. Unbiased stereological analyses of immunostained tissues showed significant Purkinje cells loss in lobule III and lobule IX of the TGI cerebellum relative to sham cerebellum, with corresponding upregulation of inflammatory and apoptotic cells. Similarly, TGI hearts revealed significant activation of inflammatory and apoptotic cells relative to sham hearts. Aberrant inflammation and apoptosis in the cerebellum and the heart of chronic TGI-exposed NHPs suggest distal secondary injuries manifesting both centrally and peripherally. These results advance our understanding on the sustained propagation of chronic secondary injuries after TGI, highlighting the need to develop therapeutic interventions targeting the brain, as well as the heart, in order to abrogate cerebral ischemia and its related co-morbidities.