Mild Systemic Inflammation has a Neuroprotective Effect After Stroke in Rats

Abstract

Stroke is accompanied by a strong inflammatory reaction in the brain. Periodontal disease is a chronic local infection which causes a systemic low grade inflammation. We hypothesized that a mild systemic inflammatory reaction as caused by periodontal disease prior to stroke onset, may exert a neuroprotective effect in a rat model of focal ischemia. To test this hypothesis, marginal periodontitis was induced by ligatures on the second maxillary molars in BB/LL Wistar rats for 3 weeks. Two weeks after periodontitis initiation, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery. After a survival time of 7 days after ischemia, rats were killed and bone loss was determined on the buccal and palatinal surfaces of the defleshed jaw. In addition, markers of systemic inflammation were determined in a different group of laboratory animals at 14 days after the onset of periodontitis. The infarct size and markers of the inflammatory reaction in the brain were determined by immunohistochemistry. We found: (i) rats with ligatures exhibited significantly more periodontal bone loss than the control rats; (ii) the development of periodontitis was associated with an elevated gene expression for several markers of systemic inflammation (interleukin-10, transforming growth factor beta 1, tumor necrosis factor alpha, interleukin-1beta and interferon gamma; (iii) rats with periodontitis and a mild systemic inflammation had a significantly reduced infarct volume and a significant reduction in the number of brain macrophages in the infarcted area. In conclusion we found that mild systemic inflammation elicited prior to stroke onset may have a neuroprotective effect in rats by reducing the infarct volume and tissue destruction by brain macrophages.

Suppression of inflammation in ischemic and hemorrhagic stroke: therapeutic options

“…Chronic prestroke inflammation can also be protective: chronic preischemic stroke infection of mice with Toxoplasma gondii reduced the subsequent proinflammatory cytokine response, improving outcome and lessening infarct size [32]. Similar results were also shown more recently following induced periodontitis in rats [33].…”

Chorioamnionitis (ChA) modifies CX3CL1 (fractalkine) production by human amniotic epithelial cells (HAEC) under normoxic and hypoxic conditions

“…The differences in CX3CL1 concentration between the groups observed under hypoxic conditions may suggest that specific “preconditioning” in the inflammatory environment in vivo was related to the acquired resistance of ChA cells to decreased oxygenation in culture. It is well documented that infection-induced inflammation may lead to local and systemic ischemia as a defense mechanism against pathogens [51,52]. Both inflammation and hypoxia may trigger TNF-α release in vivo, which has been considered a potent up-regulator of the CX3CL1/CX3CR1 signaling pathway [53,54].…”

Avances en la fisiopatología y el tratamiento de las infecciones en la fase aguda del ictus

“…Los resultados de mú ltiples modelos animales de isquemia cerebral sugieren que valores altos de mediadores proinflamatorios se asocian con mayor volumen del infarto y peor estado funcional, independientemente de la naturaleza del estímulo que produce su aumento [28][29][30][31] . En cuanto a la relació n temporal entre el estímulo inflamatorio y el episodio isqué mico, son especialmente relevantes 2 estudios que muestran que la inflamació n cró nica preexistente parece tener un efecto neuroprotector 32,33 , circunstancia que podría explicarse por la presencia de valores elevados de citocinas antiinflamatorias (especialmente IL-10), su capacidad para inhibir la inducció n de estas (especialmente factor de necrosis tumoral-a e interferó n-g) y la presencia de otras molé culas con potencial neuroprotector (por ejemplo, factores de crecimiento neural, la proteína supresora de la señ alizació n por citocinas-3, la superó xido dismutasa o el glutatió n).…”