Changes in cellular signaling patterns before and after stroke in the middle cerebral arteries of stroke prone spontaneously hypertensive rats

Abstract

BackgroundHemorrhagic stroke is associated with loss of middle cerebral artery (MCA) autoregulation in the stroke-prone spontaneously hypertensive rat (SHRsp). The signaling mechanism associated with the functional loss has yet to be defined. We hypothesize that physiological alterations coincide with changes to cerebrovascular inflammatory and contractile signaling and altered calcium signaling. METHODS: SHRsp rats were fed a high salt (4% NaCl) diet and sacrificed at 9 weeks of age for pre-stroke and after evidence of stroke for post-stroke samples. The MCAs were isolated for measuring protein levels using immunofluorescence (IF) & western blot (WB) for inflammatory signaling and contractile proteins. Tissues surrounding the MCA were analyzed for neuro-inflammation, neuronal damage, total and activated inflammatory proteins (ERK1/2 and p38MAPK), cerebrovascular contraction (PKC and MLC), and transient receptor potential V4 (TRPV4) expression. RESULTS: Our data show increase in activated inflammatory proteins after stroke with an associated decrease in expression of activated contractile proteins and TRPV4 channel expression compared to pre-stroke MCA. The post-stroke samples also show significant increase in neuro-inflammation and neuronal damage compared to pre-stroke samples. CONCLUSIONAn increase in activated/total (p38 MAPK &ERK1/2) is accompanied by a decrease in activated/total PKC & TRPV4 channel expression in post-stroke SHRsps. The decrease in vessel structural integrity and altered vascular tone of the MCAs may affect its ability to contract in response to pressure. Significant neuro-inflammation and neuronal damage in the brain tissues surrounding the MCA in post-stroke samples suggest MCA dysfunction is accompanied with neuronal and neural damage during stroke.