Lydia M Kuhl, Matthew S Jeffers, Nicolay Hristozov, Sudhir Karthikeyan, Matthew W McDonald, Aisha Hufnagel, Anthony Carter, Numa Dancause, Dale Corbett
{"title":"脑卒中后恢复与parvalbumin阳性中间神经元和周围神经元网络的关系。","authors":"Lydia M Kuhl, Matthew S Jeffers, Nicolay Hristozov, Sudhir Karthikeyan, Matthew W McDonald, Aisha Hufnagel, Anthony Carter, Numa Dancause, Dale Corbett","doi":"10.1177/15459683241309567","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>There is a critical time window of post-stroke neuroplasticity when spontaneous behavioral recovery occurs. Potential factors responsible for this heightened plasticity are the reduction of parvalbumin-immunoreactive (PV+) interneuron inhibitory signaling and the disappearance of extracellular matrix synaptic stabilizers called perineuronal net(s; PNN/PNNs).</p><p><strong>Objective: </strong>This study investigated whether behavioral recovery during this critical period following stroke is associated with changes in densities of PV+ interneurons and PNNs.</p><p><strong>Methods: </strong>Male, Sprague-Dawley rats received forelimb motor cortex stroke (n = 43) using endothelin-1, or vehicle injections (n = 44). Cohorts of rats underwent a battery of motor tests and were sacrificed within the post-stroke critical window on day 1, and 1, 2, 4, and 6 weeks. Using immunofluorescent labeling, PNNs (wisteria floribunda agglutinin; WFA+ cells), PV+ interneurons, and cells expressing both PV and PNNs were quantified in contra- and ipsilesional cortices to elucidate their spatial-temporal profiles following stroke.</p><p><strong>Results: </strong>PV+ interneuron density decreased significantly at 1-day post-stroke in the lateral ipsilesional cortex, while the density of PNNs was significantly lower up to 4 weeks post-stroke in the lateral ipsilesional cortex and at 1 and 2 weeks post-stroke in the medial ipsilesional cortex. Reduction of combined PV+/PNN signaling coincided with spontaneous behavioral recovery.</p><p><strong>Conclusions: </strong>These results suggest that post-stroke behavioral recovery corresponds to an early reduction in PV+/PNN co-labeled cells in conjunction with an early temporally-dependent reduction in PV+ interneuron signaling and chronic disappearance of PNNs. Interventions targeting PNNs or PV+ interneuron signaling have significant potential for extending the critical window of recovery following stroke.</p>","PeriodicalId":94158,"journal":{"name":"Neurorehabilitation and neural repair","volume":" ","pages":"15459683241309567"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Post-Stroke Recovery in Relation to Parvalbumin-Positive Interneurons and Perineuronal Nets.\",\"authors\":\"Lydia M Kuhl, Matthew S Jeffers, Nicolay Hristozov, Sudhir Karthikeyan, Matthew W McDonald, Aisha Hufnagel, Anthony Carter, Numa Dancause, Dale Corbett\",\"doi\":\"10.1177/15459683241309567\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>There is a critical time window of post-stroke neuroplasticity when spontaneous behavioral recovery occurs. Potential factors responsible for this heightened plasticity are the reduction of parvalbumin-immunoreactive (PV+) interneuron inhibitory signaling and the disappearance of extracellular matrix synaptic stabilizers called perineuronal net(s; PNN/PNNs).</p><p><strong>Objective: </strong>This study investigated whether behavioral recovery during this critical period following stroke is associated with changes in densities of PV+ interneurons and PNNs.</p><p><strong>Methods: </strong>Male, Sprague-Dawley rats received forelimb motor cortex stroke (n = 43) using endothelin-1, or vehicle injections (n = 44). Cohorts of rats underwent a battery of motor tests and were sacrificed within the post-stroke critical window on day 1, and 1, 2, 4, and 6 weeks. Using immunofluorescent labeling, PNNs (wisteria floribunda agglutinin; WFA+ cells), PV+ interneurons, and cells expressing both PV and PNNs were quantified in contra- and ipsilesional cortices to elucidate their spatial-temporal profiles following stroke.</p><p><strong>Results: </strong>PV+ interneuron density decreased significantly at 1-day post-stroke in the lateral ipsilesional cortex, while the density of PNNs was significantly lower up to 4 weeks post-stroke in the lateral ipsilesional cortex and at 1 and 2 weeks post-stroke in the medial ipsilesional cortex. Reduction of combined PV+/PNN signaling coincided with spontaneous behavioral recovery.</p><p><strong>Conclusions: </strong>These results suggest that post-stroke behavioral recovery corresponds to an early reduction in PV+/PNN co-labeled cells in conjunction with an early temporally-dependent reduction in PV+ interneuron signaling and chronic disappearance of PNNs. Interventions targeting PNNs or PV+ interneuron signaling have significant potential for extending the critical window of recovery following stroke.</p>\",\"PeriodicalId\":94158,\"journal\":{\"name\":\"Neurorehabilitation and neural repair\",\"volume\":\" \",\"pages\":\"15459683241309567\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-01-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurorehabilitation and neural repair\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/15459683241309567\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurorehabilitation and neural repair","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/15459683241309567","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Post-Stroke Recovery in Relation to Parvalbumin-Positive Interneurons and Perineuronal Nets.
Background: There is a critical time window of post-stroke neuroplasticity when spontaneous behavioral recovery occurs. Potential factors responsible for this heightened plasticity are the reduction of parvalbumin-immunoreactive (PV+) interneuron inhibitory signaling and the disappearance of extracellular matrix synaptic stabilizers called perineuronal net(s; PNN/PNNs).
Objective: This study investigated whether behavioral recovery during this critical period following stroke is associated with changes in densities of PV+ interneurons and PNNs.
Methods: Male, Sprague-Dawley rats received forelimb motor cortex stroke (n = 43) using endothelin-1, or vehicle injections (n = 44). Cohorts of rats underwent a battery of motor tests and were sacrificed within the post-stroke critical window on day 1, and 1, 2, 4, and 6 weeks. Using immunofluorescent labeling, PNNs (wisteria floribunda agglutinin; WFA+ cells), PV+ interneurons, and cells expressing both PV and PNNs were quantified in contra- and ipsilesional cortices to elucidate their spatial-temporal profiles following stroke.
Results: PV+ interneuron density decreased significantly at 1-day post-stroke in the lateral ipsilesional cortex, while the density of PNNs was significantly lower up to 4 weeks post-stroke in the lateral ipsilesional cortex and at 1 and 2 weeks post-stroke in the medial ipsilesional cortex. Reduction of combined PV+/PNN signaling coincided with spontaneous behavioral recovery.
Conclusions: These results suggest that post-stroke behavioral recovery corresponds to an early reduction in PV+/PNN co-labeled cells in conjunction with an early temporally-dependent reduction in PV+ interneuron signaling and chronic disappearance of PNNs. Interventions targeting PNNs or PV+ interneuron signaling have significant potential for extending the critical window of recovery following stroke.