scholarly journals Intracerebral Delivery of Brain-Derived Neurotrophic Factor Using HyStem®-C Hydrogel Implants Improves Functional Recovery and Reduces Neuroinflammation in a Rat Model of Ischemic Stroke

2018 ◽  
Vol 19 (12) ◽  
pp. 3782 ◽  
Author(s):  
Kristine Ravina ◽  
Denise Briggs ◽  
Sezen Kislal ◽  
Zuha Warraich ◽  
Tiffany Nguyen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Neurotrophic Factor ◽  
Infarct Volume ◽  
Brain Derived Neurotrophic Factor ◽  
Artery Occlusion ◽  
Sensorimotor Function ◽  
Neural Repair ◽  
Adhesive Removal ◽  
Cerebral Artery Occlusion

Ischemic stroke is a leading cause of death and disability worldwide. Potential therapeutics aimed at neural repair and functional recovery are limited in their blood-brain barrier permeability and may exert systemic or off-target effects. We examined the effects of brain-derived neurotrophic factor (BDNF), delivered via an extended release HyStem®-C hydrogel implant or vehicle, on sensorimotor function, infarct volume, and neuroinflammation, following permanent distal middle cerebral artery occlusion (dMCAo) in rats. Eight days following dMCAo or sham surgery, treatments were implanted directly into the infarction site. Rats received either vehicle, BDNF-only (0.167 µg/µL), hydrogel-only, hydrogel impregnated with 0.057 µg/µL of BDNF (hydrogel + BDNFLOW), or hydrogel impregnated with 0.167 µg/µL of BDNF (hydrogel + BDNFHIGH). The adhesive removal test (ART) and 28-point Neuroscore (28-PN) were used to evaluate sensorimotor function up to two months post-ischemia. The hydrogel + BDNFHIGH group showed significant improvements on the ART six to eight weeks following treatment and their behavioral performance was consistently greater on the 28-PN. Infarct volume was reduced in rats treated with hydrogel + BDNFHIGH as were levels of microglial, phagocyte, and astrocyte marker immunoexpression in the corpus striatum. These data suggest that targeted intracerebral delivery of BDNF using hydrogels may mitigate ischemic brain injury and restore functional deficits by reducing neuroinflammation.

Abstract WP118: The Flavanol (-)-Epicatechin Improves Functional Recovery In Mice Subjected To Experimental Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Christopher C Leonardo ◽  
Sean Robbins ◽  
Abdullah A Ahmad ◽  
Sylvain Dore
Keyword(s):  
Functional Recovery ◽  
Transcriptional Activation ◽  
Infarct Volume ◽  
Epidemiological Studies ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Adhesive Tape ◽  
Dietary Consumption ◽  
Therapeutic Doses ◽  
Cerebral Artery Occlusion

Background: Epidemiological studies indicate that flavanol consumption reduces the propensity to develop cerebrovascular disease. Available data suggest actions on multiple pro-inflammatory pathways, yet it remains unclear which pathways mediate functional recovery after stroke. Our goal is to begin identifying the mechanisms by which the flavanol (-)-epicatechin (EC) improves anatomical and functional outcomes. Based upon data from initial dose-response experiments, ongoing studies are investigating hypothesized protective pathways involving matrix metalloproteinase-mediated blood brain barrier protection and Nrf2 transcriptional activation. Methods: Male, 8-10wk old C57BL/6 mice were pretreated with EC 90m prior to permanent distal middle cerebral artery occlusion. Vehicle or EC was administered by oral gavage to mimic dietary consumption. Mice were evaluated 1, 4 and 7d post-stroke for performance on various sensorimotor tasks prior to histological assessments. Results: Initial experiments demonstrated that mice treated with 15mg/kg EC showed reduced latency to remove adhesive tape at 1d compared to vehicle controls (n=12, p<0.01). Similarly, immunoreactivity for the microglia/macrophage marker Iba1 was increased in the ipsilateral hemispheres of mice 7d after treatment with vehicle (p<0.01), whereas pretreatment with 15mg/kg blocked this effect (n=4). Mice treated with 15mg/kg also showed a trend toward reduced infarct volume relative to vehicle controls (n=5-9 per group). In subsequent reduced dosing studies, vehicle-treated mice again showed deficiencies in removing adhesive tape at 1d (n=8, p<0.01). Remarkably, mice treated with 15, 10 or 5mg/kg EC showed no deficits. Similarly, vehicle control mice showed grip strength impairments up to 7d (n=8, p<0.05) that were absent in all groups of EC-treated mice. Conclusions: Preventative administration of EC promotes functional recovery in mice subjected to experimental stroke. Investigations are underway to determine the pathways mediated by EC following administration at these therapeutic doses. Together, these data will provide insights into the potential for (-)-epicatechin as a clinical therapeutic.

Blocking A1 astrocyte conversion with semaglutide attenuates blood-brain barrier disruption in mice after middle cerebral artery occlusion

2021 ◽  
Author(s):  
Qi Zhang ◽  
Chang Liu ◽  
Rubing Shi ◽  
Huimin Shan ◽  
Lidong Deng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Signaling Pathways ◽  
Middle Cerebral Artery Occlusion ◽  
Blood Brain Barrier ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Rna Seq ◽  
Neurobehavioral Outcomes ◽  
Cerebral Artery Occlusion

Abstract Background Astrocytes play an essential role in the modulation of blood-brain barrier function. Neurological diseases induce astrocytes to transform into a neurotoxic A1 phenotype, thus exacerbating brain injury. However, the effect of A1 astrocyte on the function of BBB after stroke is unknown. Method: Adult male ICR mice (n = 78) were subjected to 90-minute transient middle cerebral artery occlusion. Immunohistochemical staining of A1 (C3d) and A2 (S100A10) was performed to characterize phenotypic changes of astrocytes overtime after stroke. Glucagon-like peptide-1 receptor agonist semaglutide was intraperitoneally injected into the mice to inhibit A1 astrocyte. Infarct volume, atrophy volume, neurobehavioral outcomes, and BBB permeability were examined. RNA-seq was adopted to explore the potential targets and signaling pathways of A1 astrocytes induced BBB dysfunction. Results Astrocytes assumed the A2 phenotype at the early stage of ischemic stroke but gradually transformed to the A1 phenotype. Semaglutide treatment reduced M1 microglia polarization and A1 astrocytes conversion after ischemic stroke (p < 0.05). Ischemia induced brain infarct volume, atrophy volume and neuroinflammation were reduced in the semaglutide treated mice. Neurobehavioral outcomes were improved compared to the control mice (p < 0.05). Further study demonstrated that semaglutide treatment reduced the gap formation of tight junction proteins ZO-1, claudin-5 and occludin, as well as IgG leakage following three days of ischemic stroke (p < 0.05). In vitro experiments revealed that A1 astrocyte-conditioned medium disrupted BBB integrity. RNA-seq further showed that A1 astrocytes were enriched in inflammatory factors and chemokines, as well as significantly modulating TNF and chemokine signaling pathways, which are closely related to barrier damage. Conclusion We concluded that astrocytes undergo a conversion from A2 phenotype to A1 phenotype overtime after ischemic stroke. A1 astrocytes aggravated BBB disruption, suggesting that block of A1 astrocytes conversion provides a novel strategy for the treatment of ischemic stroke.

scholarly journals Delayed inhibition of tonic inhibition enhances functional recovery following experimental ischemic stroke

2017 ◽  
Vol 39 (6) ◽  
pp. 1005-1014 ◽  
Author(s):  
James E Orfila ◽  
Himmat Grewal ◽  
Robert M Dietz ◽  
Frank Strnad ◽  
Takeru Shimizu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Ex Vivo ◽  
Long Term Potentiation ◽  
Artery Occlusion ◽  
Memory Impairments ◽  
Time Points ◽  
Term Potentiation ◽  
Cerebral Artery Occlusion

The current study focuses on the ability to improve cognitive function after stroke with interventions administered at delayed/chronic time points. In light of recent studies demonstrating delayed GABA antagonists improve motor function, we utilized electrophysiology, biochemistry and neurobehavioral methods to investigate the role of α5 GABAA receptors on hippocampal plasticity and functional recovery following ischemic stroke. Male C57Bl/6 mice were exposed to 45 min transient middle cerebral artery occlusion and analysis of synaptic and functional deficits performed 7 or 30 days after recovery. Our findings indicate that hippocampal long-term potentiation (LTP) is impaired 7 days after stroke and remain impaired for at least 30 days. We demonstrate that ex vivo administration of L655,708 reversed ischemia-induced plasticity deficits and importantly, in vivo administration at delayed time-points reversed stroke-induced memory deficits. Western blot analysis of hippocampal tissue reveals proteins responsible for GABA synthesis are upregulated (GAD65/67 and MAOB), increasing GABA in hippocampal interneurons 30 days after stroke. Thus, our data indicate that both synaptic plasticity and memory impairments observed after stroke are caused by excessive tonic GABA activity, making inhibition of specific GABA activity at delayed timepoints a potential therapeutic approach to improve functional recovery and reverse cognitive impairments after stroke.

scholarly journals Treatment Effects of Ischemic Stroke by Berberine, Baicalin, and Jasminoidin from Huang-Lian-Jie-Du-Decoction (HLJDD) Explored by an Integrated Metabolomics Approach

2017 ◽  
Vol 2017 ◽  
pp. 1-20 ◽  
Author(s):  
Qian Zhang ◽  
Xiaowei Fu ◽  
Junsong Wang ◽  
Minghua Yang ◽  
Lingyi Kong
Keyword(s):  
Ischemic Stroke ◽  
Treatment Effects ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
H Nmr ◽  
Abnormal Metabolism ◽  
Cerebral Artery Occlusion ◽  
First Time ◽  
Integrated Metabolomics

Berberine, baicalin, and jasminoidin were major active ingredients of Huang-Lian-Jie-Du-Decoction (HLJDD), a famous prescription of traditional Chinese medicine (TCM), which has been used for the treatment of ischemic stroke. The aim of the present study was to classify their roles in the treatment effects of ischemic stroke. A rat model of middle cerebral artery occlusion (MCAO) was constructed to mimic ischemic stroke and treatment effects of berberine, baicalin, and jasminoidin, and HLJDD was assessed by neurologic deficit scoring, infarct volume, histopathology, immunohistochemistry, biochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. In addition, the 1H NMR metabolomics approach was used to assess the metabolic profiles, which combined with correlation network analysis successfully revealed metabolic disorders in ischemic stroke concerning the treatment of the three principal compounds from HLJDD for the first time. The combined results suggested that berberine, baicalin, and jasminoidin are responsible for the effectiveness of HLJDD on the treatment of ischemic stroke by amelioration of abnormal metabolism and regulation of oxidative stress, neuron autophagy, and inflammatory response. This integrated metabolomics approach showed its potential in understanding the function of complex formulae and clarifying the role of its components in the overall treatment effects.

scholarly journals Intraventricular Brain-Derived Neurotrophic Factor Reduces Infarct Size after Focal Cerebral Ischemia in Rats

1997 ◽  
Vol 17 (5) ◽  
pp. 500-506 ◽  
Author(s):  
Wolf-R. Schäbitz ◽  
Stefan Schwab ◽  
Matthias Spranger ◽  
Werner Hacke
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Neurotrophic Factor ◽  
Cortical Neurons ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion

Brain-derived neurotrophic factor (BDNF), acting through the high-affinity receptor tyrosine kinase (TrkB), is widely distributed throughout the central nervous system and displays in vitro trophic effects on a wide range of neuronal cells, including hippocampal, cerebellar, and cortical neurons. In vivo, BDNF rescues motorneurons, hippocampal, and substantia nigral dopaminergic cells from traumatic and toxic brain injury. After transient middle cerebral artery occlusion (MCAO), upregulation of BDNF-mRNA in cortical neurons suggests that BDNF potentially plays a neuroprotective role in focal cerebral ischemia. In the current study, BDNF (2.1 μg/d) in vehicle or vehicle alone (controls) was delivered intraventricularly for 8 days, beginning 24 hours before permanent middle cerebral artery occlusion by intraluminal suture in Wistar rats (n = 13 per group). There were no differences in physiological variables recorded during surgery for the two groups. Neurological deficit (0 to 4 scale), which was assessed on a daily basis, improved in BDNF-treated animals compared with controls ( P < 0.05; analysis of variance and Scheffe's test). There were no significant differences in weight in BDNF-treated animals and controls during the experiment. After elective killing on day 7 after MCAO, brains underwent 2,3,5-triphenyltetrazolium chloride staining for calculation of the infarct volume and for histology (hematoxylin and eosin and glial fibrillary acid protein). The mean total infarct volume was 83.1 ± 27.1 mm3 in BDNF-treated animals and 139.2 ± 56.4 mm3 in controls (mean ± SD; P < 0.01, unpaired, two-tailed t-test). The cortical infarct volume was 10.8 ± 7.1 mm3 in BDNF-treated animals and 37.9 ± 19.8 mm3 in controls (mean ± SD; P < 0.05; unpaired, two-tailed t-test), whereas ischemic lesion volume in caudoputaminal infarction was not significantly different. These results show that pretreatment with intraventricular BDNF reduces infarct size after focal cerebral ischemia in rats and support the hypothesis of a neuroprotective role for BDNF in stoke.

scholarly journals Phosphodiesterase 10A is a critical target for neuroprotection in a mouse model of ischemic stroke

2021 ◽  
Author(s):  
Mustafa Caglar Beker ◽  
Ahmet B. Caglayan ◽  
Serdar Altunay ◽  
Elif Ozbay ◽  
Nilay Ates ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Cyclic Monophosphate ◽  
Tnf Α ◽  
Liquid Chromatography Tandem Mass ◽  
Inflammatory Processes ◽  
Phosphodiesterase 10A ◽  
Cerebral Artery Occlusion ◽  
Blood Brain Barrier Integrity

Abstract Phosphodiesterase 10A (PDE10A) hydrolyzes adenosine 3′,5′-cyclic monophosphate (cAMP) and guanosine 3′,5′-cyclic monophosphate (cGMP). It is highly expressed in the striatum. Recent evidence implied that PDE10A may be involved in the inflammatory processes following injury, such as ischemic stroke. Its role in ischemic injury was unknown. Herein, we exposed mice to 90 or 30 min middle cerebral artery occlusion, followed by the delivery of the highly selective PDE10A inhibitor TAK-063 (0.3 mg/kg or 3 mg/kg) immediately after reperfusion. Animals were sacrificed after 24 or 72 hours, respectively. Both TAK-063 doses enhanced neurological function, reduced infarct volume, increased neuronal survival, reduced brain edema, and increased blood-brain barrier integrity, alongside cerebral microcirculation improvements. Post-ischemic neuroprotection was associated with increased phosphorylation (i.e., activation) of pro-survival Akt, Erk-1/2 and GSK-3α/β, decreased phosphorylation (i.e., activation) of pro-survival mTOR, increased HIF-1α, MMP-9 and anti-apoptotic Bcl-xL abundance, and reduced pro-apoptotic Bax abundance. Interestingly, PDE10A inhibition reduced inflammatory cytokines/chemokines, including IFN-γ and TNF-α, analyzed by planar surface immunoassay. In addition, liquid chromatography-tandem mass spectrometry revealed 40 proteins were significantly altered by TAK-063. Our study established PDE10A as a target for ischemic stroke therapy.

Influence of simultaneous pressor and vasodilatory agents on the evolution of infarct growth in experimental acute middle cerebral artery occlusion

2020 ◽  
pp. neurintsurg-2020-016539
Author(s):  
Niloufar Saadat ◽  
Gregory A Christoforidis ◽  
Yong Ik Jeong ◽  
Mira Liu ◽  
Alexey Dimov ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Volume Growth ◽  
Artery Occlusion ◽  
Blood Pressure Elevation ◽  
And Control ◽  
Cerebral Artery Occlusion

BackgroundThis study sought to test the hypothesis that simultaneous central blood pressure elevation and potent vasodilation can mitigate pial collateral-dependent infarct growth in acute ischemic stroke.MethodsTwenty mongrel canines (20–30 kg) underwent permanent middle cerebral artery occlusion (MCAO). Eight subjects received continuous infusion of norepinephrine (0.1–1.5200 µg/kg/min; titrated to a median of 34 mmHg above baseline mean arterial pressure) and hydralazine (20 mg) starting 30 min following MCAO. Pial collateral recruitment was scored prior to treatment and used to predict infarct volume based on a previously reported parameterization. Serial diffusion magnetic resonance imaging (MRI) acquisitions tracked infarct volumes over a 4-hour time frame. Infarct volumes and infarct volume growth between treatment and control groups were compared with each other and to predicted values. Fluid-attenuated inversion recovery (FLAIR) MRI, susceptibility weighted imaging (SWI), and necropsy findings were included in the evaluation.ResultsDifferences between treatment and control group varied by pial collateral recruitment based on indicator-variable regression effects analysis with interaction confirmed by regression model fit. Benefit in treatment group was only in subjects with poor collaterals which had 35.7% less infarct volume growth (P=0.0008; ANOVA) relative to controls. Measured infarct growth was significantly lower than predicted by the model (linear regression partial F-test, slope P<0.001, intercept=0.003). There was no evidence for cerebral hemorrhage or posterior reversible encephalopathy syndrome.ConclusionOur results indicate that a combination of norepinephrine and hydralazine administered in the acute phase of ischemic stroke mitigates infarct evolution in subjects with poor but not good collateral recruitment.

scholarly journals A Novel Na + -K + -Cl − Cotransporter 1 Inhibitor STS66* Reduces Brain Damage in Mice After Ischemic Stroke

Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 1021-1025 ◽  
Author(s):  
Huachen Huang ◽  
Mohammad Iqbal H. Bhuiyan ◽  
Tong Jiang ◽  
Shanshan Song ◽  
Sandhya Shankar ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Large Vessel ◽  
Neurological Deficits ◽  
Ang Ii ◽  
Cerebral Artery Occlusion

Background and Purpose— Inhibition of brain NKCC1 (Na + -K + -Cl − cotransporter 1) with bumetanide (BMT) is of interest in ischemic stroke therapy. However, its poor brain penetration limits the application. In this study, we investigated the efficacy of 2 novel NKCC1 inhibitors, a lipophilic BMT prodrug STS5 (2-(Dimethylamino)ethyl 3-(butylamino)-4-phenoxy-5-sulfamoyl-benzoate;hydrochloride) and a novel NKCC1 inhibitor STS66 (3-(Butylamino)-2-phenoxy-5-[(2,2,2-trifluoroethylamino)methyl]benzenesulfonamide), on reducing ischemic brain injury. Methods— Large-vessel transient ischemic stroke in normotensive C57BL/6J mice was induced with 50-min occlusion of the middle cerebral artery and reperfusion. Focal, permanent ischemic stroke in angiotensin II (Ang II)–induced hypertensive C57BL/6J mice was induced by permanent occlusion of distal branches of middle cerebral artery. A total of 206 mice were randomly assigned to receive vehicle DMSO, BMT, STS5, or STS66. Results— Poststroke BMT, STS5, or STS66 treatment significantly decreased infarct volume and cerebral swelling by ≈40% to 50% in normotensive mice after transient middle cerebral artery occlusion, but STS66-treated mice displayed better survival and sensorimotor functional recovery. STS5 treatment increased the mortality. Ang II–induced hypertensive mice exhibited increased phosphorylatory activation of SPAK (Ste20-related proline alanine-rich kinase) and NKCC1, as well as worsened infarct and neurological deficit after permanent distal middle cerebral artery occlusion. Conclusions— The novel NKCC1 inhibitor STS66 is superior to BMT and STS5 in reducing ischemic infarction, swelling, and neurological deficits in large-vessel transient ischemic stroke, as well as in permanent focal ischemic stroke with hypertension comorbidity.

scholarly journals Image-based stroke rat brain atrophy volume and infarct volume computation

2020 ◽  
Vol 76 (12) ◽  
pp. 10090-10121
Author(s):  
Yung-Kuan Chan ◽  
Chun-Fu Hong ◽  
Meng-Hsiun Tsai ◽  
Ya-Lan Chang ◽  
Ping-Hsuan Sun
Keyword(s):  
Ischemic Stroke ◽  
Rat Brain ◽  
Brain Slice ◽  
Infarct Volume ◽  
Brain Slices ◽  
Artery Occlusion ◽  
Tetrazolium Chloride ◽  
Rat Brain Slice ◽  
Cerebral Artery Occlusion ◽  
The Brain

Abstract Stroke is one of the leading causes of death as well as results in a massive economic burden for society. Stroke is a cerebrovascular disease mainly divided into two types: ischemic stroke and hemorrhagic stroke, which, respectively, refer to the partial blockage and bleeding inside brain blood vessels. Both stroke types lead to nutrient and oxygen deprivation in the brain, which ultimately cause brain damage or death. This study focuses on ischemic stroke in rats with middle cerebral artery occlusion (MCAO) as experimental subjects, and the volumes of infarct and atrophy are calculated based on the brain slice images of rat brains stained with 2,3,5-triphenyl tetrazolium chloride. In this study, a stroke rat brain infarct and atrophy volumes computation system (SRBIAVC system) is developed to segment the infarcts and atrophies from the rat brain slice images. Based on the segmentation results, the infarct and atrophy volumes of a rat brain can be computed. In this study, 168 images of brain slices cut from 28 rat brains with MCAO are used as the test samples. The experimental results show that the segmentation results obtained by the SRBIAVC system are close to those obtained by experts.

scholarly journals Mesenchymal Stem Cells Expressing Brain-Derived Neurotrophic Factor Enhance Endogenous Neurogenesis in an Ischemic Stroke Model

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Chang Hyun Jeong ◽  
Seong Muk Kim ◽  
Jung Yeon Lim ◽  
Chung Heon Ryu ◽  
Jin Ae Jun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Functional Recovery ◽  
Subventricular Zone ◽  
Neurotrophic Factor ◽  
Therapeutic Potential ◽  
Brain Derived Neurotrophic Factor ◽  
Neurological Deficits ◽  
Therapeutic Benefits

Numerous studies have reported that mesenchymal stem cells (MSCs) can ameliorate neurological deficits in ischemic stroke models. Among the various hypotheses that have been suggested to explain the therapeutic mechanism underlying these observations, neurogenesis is thought to be critical. To enhance the therapeutic benefits of human bone marrow-derived MSCs (hBM-MSCs), we efficiently modified hBM-MSCs by introduction of the brain-derived neurotrophic factor (BDNF) gene via adenoviral transduction mediated by cell-permeable peptides and investigated whetherBDNF-modified hBM-MSCs (MSCs-BDNF) contributed to functional recovery and endogenous neurogenesis in a rat model of middle cerebral artery occlusion (MCAO). Transplantation of MSCs induced the proliferation of 5-bromo-2′-deoxyuridine (BrdU-) positive cells in the subventricular zone. Transplantation of MSCs-BDNF enhanced the proliferation of endogenous neural stem cells more significantly, while suppressing cell death. Newborn cells differentiated into doublecortin (DCX-) positive neuroblasts and Neuronal Nuclei (NeuN-) positive mature neurons in the subventricular zone and ischemic boundary at higher rates in animals with MSCs-BDNF compared with treatment using solely phosphate buffered saline (PBS) or MSCs. Triphenyltetrazolium chloride staining and behavioral analysis revealed greater functional recovery in animals with MSCs-BDNF compared with the other groups. MSCs-BDNF exhibited effective therapeutic potential by protecting cell from apoptotic death and enhancing endogenous neurogenesis.

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