Ischemic damage and early inflammatory infiltration are different in the core and penumbra lesions of rat brain after transient focal cerebral ischemia

• Published in: Journal of neuroimmunology Vol. 324; pp. 35 - 42
• Main Authors: Horváth, Emőke, Huțanu, Adina, Chiriac, Liviu, Dobreanu, Minodora, Orădan, Alex, Nagy, Előd-Ernő
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2018
• Subjects: Cerebral ischemia; COX-2; Digital morphometry; Early inflammatory infiltrate; FXIII; M1/M2 macrophages; COX-2; MRI; iNOS2; PMNs; I; MPO; S; FXIII; CD15; PGE-2; Arg1; DAB; Early inflammatory infiltrate; H&E; MMPs; TTDS; TBV; MCA; IV; Cerebral ischemia; CV; CD3; CD68; MMP-9; tMCAO; Digital morphometry; M1/M2 macrophages
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2018.08.002

Clinical and experimental observations emphasize that inflammation is a direct risk factor for stroke. We performed a detailed histological and immunohistochemical analysis, assisted by digital morphometry, to compare the representative brain lesions in the ischemic core and penumbra in a rat model. Focal neuronal necrosis and degeneration were significantly more intense in the core, whereas inflammatory infiltration, MPO, CD68, CD3, FXIII, Cox-2, iNOS2, Arg-1 expressions were stronger in the penumbra. Our findings indicate that neuroinflammation affects the penumbra more than the core and suggest that targeted modulation of the cellular infiltrate could be exploited to save brain volume. According to the degree of injury, the brain tissue involved in acute ischemic stroke can be structured in two zones: the ischemic core and the penumbra. Neurons in the core are the most affected, but the penumbra is also exposed to hypoxia and has an increased risk of being merged into the ischemic core. The ischemic lesions in the penumbra are dominated by the invasion of inflammatory cells (activated microglia and blood-derived macrophages, polymorphonuclear neutrophils, and T-lymphocytes). Modulation of this pathway represent a potential therapeutical target to reduce the extent of the irreversible tissue damage. [Display omitted] •Transient middle cerebral artery occlusion triggers neuronal death and degeneration accompanied by early neuroinflammation.•The most important ischemic region in the brain: the core and penumbra show different lesions and morphology•Neuronal necrosis and degeneration are more intense in the core, while inflammatory infiltration is stronger in penumbra•MPO, CD68, iNOS2, Arg-1, FXIII, CD3 and Cox-2 expressions are significantly higher in penumbra•Inflammation plays a dual role in the postischemic timeline, its modulation might be of therapeutical interest