Moreover, they provide trophic support to tissue at risk in the penumbra surrounding the infarct area, enhance vasculogenesis, and help promote survival, migration, and differentiation of the endogenous precursor cells after stroke.
Here we show for the first time that treatment with TRC051384 significantly reduces stroke associated neuronal injury (87% reduction in area of penumbra recruited to infarct, and 25% reduction in brain edema) and disability in a rat model of transient ischemic stroke even when administered 8 hours post onset of ischemia.
The presence of apoptotic neurons in the ischemic penumbra and perihematoma area may account for poor prognosis, but whether the highly variable stroke outcome reflects differences in genetic susceptibility to apoptosis is elusive.
This review highlights preclinical microarray findings of the ischemic brain, discusses the transcriptome of cerebral preconditioning and emphasizes the importance of further characterizing the role of the neurovascular unit and peripheral white blood cells in mediating stroke damage and repair within the penumbra.
A previous animal study demonstrated an increased expression of the endocannabinoid receptor 1 (CB1R) in the penumbra area surrounding the ischemic core, suggesting a crucial role in inflammation/reperfusion after stroke.
The results revealed that SIRT2 was mainly expressed in the cytoplasm and neurites of neurons in the brains of normal subjects, while an elevated expression and nuclear translocation of SIRT2 were detected in the ischemic penumbra of cerebral stroke.
With these variables, clear definitions of irreversible tissue damage and of critically hypoperfused but potentially salvageable tissue (i.e., the penumbra) in stroke patients can be achieved.
Variation in collateral extent significantly alters infarct volume expansion, transiently affects perfusion and diffusion magnetic resonance imaging signatures, and impacts salvage of ischemic penumbra after stroke onset.
Our experience indicates that CEA performed early after IVT for acute ischemic stroke, aiming not only to reduce the risk of stroke recurrence but also to achieve neurological improvement by reperfusion of the ischemic penumbra, may be safe and can lead to favorable outcomes.
Improvement in acute 24-hour National Institutes of Health Stroke Scale was also significantly related to the degree of reperfused penumbra (<i>R</i><sup>2</sup>, 0.31; P<0.0001).
Further research to refine and validate these techniques may enable their use as MRI-based surrogate markers of the ischemic penumbra for selecting stroke patients for interventional treatment strategies.
This review describes the current application of the photothrombotic stroke model for the study of cellular and molecular mechanisms of stroke development and ischemic penumbra formation, as well as for the search of anti-stroke drugs.
While identification of the ischemic infarct, and the infarct/penumbra boundary is relatively trivial using classical histology and microscopy techniques, accurately assessing the penetration of the penumbra zone into undamaged brain tissue, and evaluating the magnitude of chemical alterations in the penumbra, has long been a major challenge to the stroke research field.
We prospectively recruited patients with (i) acute middle-cerebral artery stroke; (ii) penumbra present on CT perfusion obtained <4.5 h of stroke onset; and (iii) early neurological recovery as a marker of penumbral salvage.
In AIS patients (n = 55), baseline computerized tomography (CT) was performed ≤ 8 h from symptom onset, whereas CT determination of reperfusion/recanalization was assessed at 24 h. Multiple linear and logistic regression models were used to correlate reperfusion/recanalization with radiological (i.e., hemorrhagic transformation, ischemic core, and penumbra volumes) and clinical outcomes (assessed as National Institutes of Health Stroke Scale [NIHSS] reduction ≥ 8 points or a NIHSS ≤ 1 at 24 h and as modified Rankin Scale [mRS] < 2 at 90 days).