In addition to thrombolysis, tissue plasminogen activator (tPA) can evoke neurorestorative processes. We therefore investigated the therapeutic effect of subacute intranasal administration of tPA post stroke on neurological recovery and on corticospinal innervation in mice. A transgenic mouse line, in which the pyramidal neurons and corticospinal tract (CST) axons are specifically labeled by yellow fluorescent protein (YFP) was employed. Adult CST-YFP mice were subjected to right unilateral middle cerebral artery occlusion (MCAo), and were randomly divided into groups treated with saline or tPA intranasally in the subacute phase. Pseudorabies virus (PRV)-614-monomeric red fluorescent protein (RFP) was injected into the left forelimb. The cervical spinal cord and brain were processed for fluorescent microscopy to detect YFP and RFP labeling. Primary embryonic neurons were cultured with tPA at different concentrations. Neurite length and branch numbers were then measured. In vivo, subacute tPA treatment significantly enhanced functional recovery (p < 0.05), and increased CST density in the denervated gray matter, and in the numbers of PRV-labeled neurons in bilateral cortices. The behavioral performance was significantly correlated with axonal density in the denervated spinal cord. In vitro, both neurite length and branch numbers significantly increased with concentration of tPA (p < 0.05). Our results demonstrate that tPA dose-dependently increases neurite outgrowth and branching of cultured cortical neurons. Subacute intranasal administration of tPA may provide enhance neurological recovery after stroke by promoting CST axonal remodeling.
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http://dx.doi.org/10.1016/j.expneurol.2018.03.001 | DOI Listing |
Vaccines (Basel)
December 2024
Research Institute for Biological Safety Problems, Gvardeiskiy 080409, Kazakhstan.
The research conducted in this preclinical study assesses QazCovid-live, a live attenuated COVID-19 vaccine created in Kazakhstan, by conducting preclinical evaluations of safety, immunogenicity, and allergenicity in various animal models, including mice, rats, hamsters, and guinea pigs. The vaccine, developed by attenuating SARS-CoV-2 via numerous Vero cell passages, had no significant adverse effects in acute and subacute toxicity assessments, even at elevated dosages. Allergenicity testing indicated the absence of both immediate and delayed hypersensitivity reactions.
View Article and Find Full Text PDFCell Rep Med
November 2024
Department of Clinic Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China. Electronic address:
Although stroke is a frequent cause of permanent disability, our ability to promote stroke recovery is limited. Here, we design a small-molecule stroke recovery promoting agent that works by dissociating γ-aminobutyric acid (GABA) transporter 1 (GAT-1) from syntaxin1A (Synt1A), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. Stroke induces an increase in GAT-1-Synt1A interaction in the subacute phase, a critical period for functional recovery.
View Article and Find Full Text PDFNeurology
July 2024
From the Departments of Neurology (A.C.M., J.C.G.-M.), Radiology (J.J.G.M., L.A.M.), and Neurosurgery (A.B.G.), Basurto University Hospital, Osakidetza Basque Health Service, Bilbao, Spain.
Cocaine-induced midline destructive lesions (CIMDL) are a rare complication of chronic intranasal cocaine use involving the centrofacial mucosal structures, often with nasal septum perforation and, in severe cases, involvement of neurocranial structures. Patients present with nasal obstruction, epistaxis, facial pain, nasal ulcerative lesions with crusting, and septal and palate perforation causing dysphagia and nasal reflux. CNS involvement is uncommon.
View Article and Find Full Text PDFExp Neurol
September 2024
Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital, Southwest Medical University, Luzhou, China. Electronic address:
The activation of glial cells is intimately associated with the pathophysiology of neuroinflammation and white matter injury (WMI) during both acute and chronic phases following subarachnoid hemorrhage (SAH). The complement C3a receptor (C3aR) has a dual role in modulating inflammation and contributes to neurodevelopment, neuroplasticity, and neurodegeneration. However, its impact on WMI in the context of SAH remains unclear.
View Article and Find Full Text PDFVet World
March 2024
Department of Linguistics and Intercultural Communication of the Faculty of Distance Learning and Part-Time Education of Moscow State Linguistic University, 119034 Moscow, Russia.
Background And Aim: The pathogenesis of staphylococcal infections is mediated by virulence factors, such as enzymes, toxins, and biofilms, which increase the resistance of microorganisms to host immune system evasion. Testing and searching for standardized multi-level algorithms for the indication and differentiation of biofilms at the early stages of diagnosis will contribute to the development of preventive measures to control the critical points of technology and manage dangerous risk factors for the spread of infectious diseases. This research aimed to study the main stages of s biofilm formation in experiments and to analyze the dynamics of respiratory syndrome development in chickens infected with these bacteria.
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