Brain repair mechanisms after cell therapy for stroke

Stem cell grafting can promote glial repair of adult stroke injuries during the subacute wound healing phase, but graft survival and glial repair outcomes are perturbed by lesion severity and mode of injury. To better understand how stroke lesion environments alter the functions of cell grafts, we employed optical coherence tomography (OCT) to longitudinally image mouse cortical photothrombotic ischemic strokes treated with allogeneic neural progenitor cell (NPC) grafts. OCT angiography, signal intensity, and signal decay resulting from optical scattering were assessed at multiple timepoints across two weeks in mice receiving an NPC graft or an injection of saline at two days after stroke. OCT scattering information revealed pronounced axial lesion contraction that naturally occurred throughout the subacute wound healing phase that was not modified by either NPC or saline treatment. By analyzing OCT signal intensity along the coronal plane, we observed dramatic contraction of the cortex away from the imaging window in the first week after stroke which impaired conventional OCT angiography but which enabled the detection of NPC graft-induced glial repair. There was moderate, but variable, NPC graft survival at photothrombotic strokes at two weeks which was inversely correlated with acute stroke lesion sizes as measured by OCT prior to treatment, suggesting a prognostic role for OCT imaging and reinforcing the dominant effect of lesion size and severity on graft outcome. Overall, our findings demonstrate the utility of OCT imaging for both tracking and predicting natural and treatment-directed changes in ischemic stroke lesion cores.

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Neurovascular dysfunction in psychiatric disorders: Underlying mechanisms and therapeutic approaches

Sanches,

Simões,

Baptista

et al. 2024

Eur J Clin Investigation

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BackgroundNeurovascular interfaces, specifically the blood–brain barrier (BBB) and blood–retinal barrier (BRB), play pivotal roles in maintaining the homeostasis of the central nervous system (CNS). For a long time, these structures were seen only as a way of protection, but we currently know that they have a critical role in CNS (dys)function. Several studies have identified neurovascular alterations in early stages of brain and eye diseases, contributing to the pathophysiology of such conditions. More recently, interesting data have also highlighted the importance of neurovasculature in psychiatric disorders.MethodsUsing the PubMed database, we brought together the evidence concerning the changes in BBB and BRB under psychiatric conditions, with a focus on anxiety, major depressive disorder (MDD), attention‐deficit/hyperactivity disorder (ADHD) and drug abuse, specifically related with methamphetamine (METH) and cocaine consumption.ResultsWe summarized the main findings obtained from in vitro and animal studies, as well as clinical research that has been undertaken to identify neurovascular abnormalities upon such neuropsychiatric disorders. The drivers of barrier alterations were examined, namely the role of neuroinflammation, while reporting putative barrier‐associated biomarkers of these disorders.ConclusionThis review underscores the critical need for a deeper understanding of BBB and BRB function in neuropsychiatric conditions and their potential as therapeutic targets while elucidating the key players involved. The innovative approaches to managing these complex disorders are also addressed while bridging the gap concerning what is currently known regarding the association between neuropsychiatric conditions and their vascular implications.

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Brain repair mechanisms after cell therapy for stroke

Cited by 3 publications

References 264 publications

Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions

Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions

Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions

Neurovascular dysfunction in psychiatric disorders: Underlying mechanisms and therapeutic approaches

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