Acute passive static stretching did not seem to increase the CTF.
Ischemic stroke is a debilitating neurological disease most commonly resulting from an occlusion within the cerebral vasculature. Ischemia/reperfusion injury is oftentimes a consequence of stroke, characterized by oxidative stress, neuroinflammation, and the activation of surrounding glial cells following restoration of blood supply. Astrocytes are regarded as the most prominent glial cell in the brain and, under pathologic conditions, display, among other pathologies, activated (GFAP) relatively proportional to the degree of reactivity. The primary objective of the study was to determine the temporal profile of astrocyte reactivity following ischemic stroke. Thirty-four Sprague-Dawley rats were assigned to surgery consisting of either 90-min middle cerebral artery occlusion (MCAo) or sham surgery. Animals were sub-grouped by postoperative euthanization day; 2 days (n = 10), 4 days (n = 11), and 7 days (n = 13). Fluorescence microscopy and densitometry were utilized to quantify GFAP immunoreactivity, which indicated a non-linear relationship following ischemia/reperfusion. Results demonstrated substantially higher GFAP levels in MCAo groups than in sham, with peak GFAP reactivity being shown in the brains of rats euthanized on day 4. These findings are applicable to future research, especially in the investigation of interventions that target reactive astrocytes following ischemic injury.
A major drawback of current stroke treatment strategies (such as the use of tPA) includes time sensitivity to achieve maximum therapeutic efficacy. Alternative treatments include less time-sensitive approaches and utilize in vivo reprogramming of resident reactive astrocytes to repopulate the lost neurons in sufficient numbers. In this study, we tested whether a transcription factor, hSOX2, when expressed under a glial cell-specific GFAP promoter, could sufficiently reprogram astrocytes in and around the infarct to enhance their differentiation into neurons. To achieve delivery of the hSOX2 gene, we utilize PAMAM dendrimers, which are nanomolecules with a well-established capacity of delivering drugs/ large biomolecules to the brain across the BBB and confer intrinsic anti-inflammatory properties. Dendrimers are comprised of an interior dendritic structure with modifiable sizes, and an exterior surface with functional surface groups. The G4 PAMAM dendrimers used in this study has 10% of the surface covered with amine groups and 90% of the surface covered with hydroxyl groups (G4-90/10). These dendrimers are less toxic and readily form complexes with plasmids up to 14 kb in size (dendriplex) and successfully deliver cargo in vitro and in vivo . Four days following stroke inductions in Sprague Dawley rats via MCAo, the hSOX2 dendriplex was injected into the ipsilateral corpus callosum. A battery of behavior tests, such as cylinder and ladder tasks, were used to assess motor abilities of the treated and untreated stroked and sham-operated control rats. Moreover, the animals underwent In vivo Imaging System to confirm the presence of dendriplex in the brain. Five weeks following the injections, the brains were collected and processed, using immunohistochemistry, to detect the complex and measure the amount of hSOX2 gene expression. The size of the brain infarct was measured using the conventional H&E staining. Our results indicated that the dendrimers were able to deliver the hSOX2 gene to the stroke brain and this significantly reduced motor deficits, relative to untreated stroked rats. These results indicated that PAMAM dendrimers effectively deliver genes into the brain and that the hSOX2 gene can successfully reduce motor deficits following stroke.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.