AimsWe have recently created an age-dependent hypertensive-mono-arthritic animal model from the stroke-resistant spontaneously hypertensive rat to model populations with autoimmune disease who are hypertensive and are prone to stroke. The model exhibits signs of hemorrhagic stroke (HS) subsequent to chronic inflammation and hypertension. HS is also associated with the inability of middle cerebral arteries to undergo pressure dependent constriction (PDC). We investigated alterations in the cerebrovasculature of our hypertensive mono-arthritic animals that develop stroke.Main MethodsAnimals were fed either a high salt diet (HSD) (4% NaCl) or Purina chow (0.58% NaCl) from weaning. Complete Freund’s Adjuvant (CFA) was injected into the left hind paw at 21–28 weeks; controls received saline and histological and functional studies were performed.ResultsBrain damage was more prominent with the high salt, with inflammation exacerbating the damage. High salt alone significantly decreased middle cerebral artery’s (MCA’s) ability to undergo PDC. Inflammation significantly decreased the ability of cerebrovasculature to respond to pressure step in the regular salt diet. The responses to vasoactive peptides were also significantly attenuated in both inflamed groups regardless of diet.ConclusionInduction of chronic systemic inflammation increases brain damage, and affect the MCA’s vasogenic function, decreasing its ability to respond to intraluminal pressure. HSD further exacerbates organ damage associated with chronic inflammation, further compromising cerebrovascular function, and likely increasing the incidence of intracerebral hemorrhage and injury.
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.
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