scholarly journals Mature Adult Mice With Exercise-Preconditioning Show Better Recovery After Intracerebral Hemorrhage

Stroke ◽  
2021 ◽  
Vol 52 (5) ◽  
pp. 1861-1865
Author(s):  
Keita Kinoshita ◽  
Gen Hamanaka ◽  
Ryo Ohtomo ◽  
Hajime Takase ◽  
Kelly K. Chung ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Intracerebral Hemorrhage ◽  
Treadmill Exercise ◽  
Neurological Deficits ◽  
Multiple Time ◽  
Lesion Volume ◽  
Soluble Factors ◽  
Mature Adult ◽  
Adult Mice ◽  
Exercise Preconditioning

Background and Purpose: Physical exercise offers therapeutic potentials for several central nervous system disorders, including stroke and cardiovascular diseases. However, it is still mostly unknown whether and how exercise preconditioning affects the prognosis of intracerebral hemorrhage (ICH). In this study, we examined the effects of preconditioning on ICH pathology in mature adult mice using treadmill exercise. Methods: Male C57BL/6J (25-week old) mice were subjected to 6 weeks of treadmill exercise followed by ICH induction. Outcome measurements included various neurological function tests at multiple time points and the assessment of lesion volume at 8 days after ICH induction. In addition, plasma soluble factors and phagocytotic microglial numbers in the peri-lesion area were also measured to determine the mechanisms underlying the effects of exercise preconditioning. Results: The 6-week treadmill exercise preconditioning promoted recovery from ICH-induced neurological deficits in mice. In addition, mice with exercise preconditioning showed smaller lesion volumes and increased numbers of phagocytotic microglia. Furthermore, the levels of several soluble factors, including endostatin, IGFBP (insulin-like growth factor-binding protein)-2 and -3, MMP (matrix metallopeptidase)-9, osteopontin, and pentraxin-3, were increased in the plasma samples from ICH mice with exercise preconditioning compared with ICH mice without exercise. Conclusions: These results suggest that mice with exercise preconditioning may suffer less severe injury from hemorrhagic stroke, and therefore, a habit of physical exercise may improve brain health even in middle adulthood.

scholarly journals Remote Ischemic Postconditioning vs. Physical Exercise After Stroke: an Alternative Rehabilitation Strategy?

2021 ◽  
Author(s):  
Xiaokun Geng ◽  
Qingzhu Wang ◽  
Hangil Lee ◽  
Christian Huber ◽  
Melissa Wills ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Treadmill Exercise ◽  
Infarct Volume ◽  
Ischemic Postconditioning ◽  
Synaptic Proteins ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Neurobehavioral Function ◽  
Remote Ischemic Postconditioning ◽  
Function Tests

AbstractThere remain debates on neuroprotection and rehabilitation techniques for acute ischemic stroke patients. Therapeutic physical exercise following stroke has shown promise but is challenging to apply clinically. Ischemic conditioning, which has several clinical advantages, is a potential neuroprotective method for stroke rehabilitation that is less understood. In the present study, the rehabilitative properties and mechanisms of physical exercise and remote ischemic postconditioning (RIPostC) after stroke were compared and determined. A total of 248 adult male Sprague-Dawley rats were divided into five groups: (1) sham, (2) stroke, (3) stroke with intense treadmill exercise, (4) stroke with mild treadmill exercise, and (5) stroke with RIPostC. Focal ischemia was evaluated by infarct volume and neurological deficit. Long-term functional outcomes were represented through neurobehavioral function tests: adhesive removal, beam balance, forelimb placing, grid walk, rota-rod, and Morris water maze. To further understand the mechanisms underlying neurorehabilitation and verify the presence thereof, we measured mRNA and protein levels of neuroplasticity factors, synaptic proteins, angiogenesis factors, and regulation molecules, including HIF-1α, BDNF, TrkB, and CREB. The key role of HIF-1α was elucidated by using the inhibitor, YC-1. Both exercise intensities and RIPostC significantly decreased infarct volumes and neurological deficits and outperformed the stroke group in the neurobehavioral function tests. All treatment groups showed significant increases in mRNA and protein expression levels of the target molecules for neurogenesis, synaptogenesis, and angiogenesis, with intermittent further increases in the RIPostC group. HIF-1α inhibition nullified most beneficial effects and indicative molecule expressions, including HIF-1α, BDNF, TrkB, and CREB, in both procedures. RIPostC is equally, or superiorly, effective in inducing neuroprotection and rehabilitation compared to exercise in ischemic rats. HIF-1α likely plays an important role in the efficacy of neuroplasticity conditioning, possibly through HIF-1α/BDNF/TrkB/CREB regulation.

Abstract TP111: Haptoglobin Improves Intracerebral Hemorrhage Outcomes by Modulating Angiogenic Responses

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Jenna Leclerc ◽  
Tina Esfandiary ◽  
Sylvain Dore
Keyword(s):  
Intracerebral Hemorrhage ◽  
Tissue Repair ◽  
Autologous Blood ◽  
Healing Process ◽  
Acute Injury ◽  
Neurological Deficits ◽  
Lesion Volume ◽  
Oxidative Potential ◽  
Ambulatory Ability ◽  
The Brain

Intracerebral hemorrhage (ICH) most often occurs spontaneously and is one of the most devastating stroke subtypes. Following ICH, toxic blood components must be cleared from the brain as part of the tissue repair/scar formation healing process. Angiogenesis is a key physiologic mechanism that facilitates tissue repair following acute injury, but must be tightly regulated to prevent excessive activity and deleterious consequences. After ICH, regulation of angiogenesis within the appropriate range in injured brain regions would allow for delivery of glucose and oxygen to support the energy-requiring reparative processes and facilitate the necessary entry of peripheral cells involved. Haptoglobin (Hp) is an acute phase protein that binds extracorpuscular hemoglobin, thereby directly reducing its oxidative potential, and Hp has also been shown to have potent angiogenic, vasculogenic, and wound healing properties. Using the autologous blood model of ICH, we have shown that Hp overexpression significantly improves ICH outcomes and reduces oxidative processes. Here, we aimed to confirm our previous results and further characterize the mechanisms by which Hp exerts these neuroprotective effects. Hp was overexpressed in the brain using adeno-associated viral vectors and ICH was induced using the collagenase-induced spontaneous bleeding model, which is accompanied by clinically relevant intraventricular hemorrhage. In line with our previous study, Hp-overexpressing mice demonstrate significantly smaller lesion volumes (p<0.01) and less residual blood (p<0.05). This reduced ICH-induced brain injury is accompanied by trends towards improved ambulatory ability and less focal neurological deficits at 72h post-ICH (p<0.07). Hp-overexpressing mice have significantly reduced PECAM-1 expression and tend to have less VEGF immunoreactivity. After correcting for lesion volume, Hp-overexpressing mice retain the decreased PECAM-1 expression, but VEGF expression is increased, collectively suggesting a direct role of Hp in positively modulating angiogenesis after ICH. Hp therapy could represent a new treatment strategy for ICH through a multifactorial mechanism that includes the modulation of important angiogenic processes.

scholarly journals The anesthetic approach for endovascular recanalization therapy depends on the lesion site in acute ischemic stroke

2021 ◽  
Author(s):  
Kilian Fröhlich ◽  
Gabriela Siedler ◽  
Svenja Stoll ◽  
Kosmas Macha ◽  
Thomas M. Kinfe ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Acute Ischemic Stroke ◽  
Cerebral Artery ◽  
Posterior Circulation ◽  
Neurological Deficits ◽  
Stroke Severity ◽  
Lesion Volume ◽  
Middle Cerebral Artery Territory ◽  
Cerebral Lesion

Abstract Purpose Endovascular therapy (EVT) of large-vessel occlusion in acute ischemic stroke (AIS) may be performed in general anesthesia (GA) or conscious sedation (CS). We intended to determine the contribution of ischemic cerebral lesion sites on the physician’s decision between GA and CS using voxel-based lesion symptom mapping (VLSM). Methods In a prospective local database, we sought patients with documented AIS and EVT. Age, stroke severity, lesion volume, vigilance, and aphasia scores were compared between EVT patients with GA and CS. The ischemic lesions were analyzed on CT or MRI scans and transformed into stereotaxic space. We determined the lesion overlap and assessed whether GA or CS is associated with specific cerebral lesion sites using the voxel-wise Liebermeister test. Results One hundred seventy-nine patients with AIS and EVT were included in the analysis. The VLSM analysis yielded associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas. Stroke severity and lesion volume were significantly higher in the GA group. The prevalence of aphasia and aphasia severity was significantly higher and parameters of vigilance lower in the GA group. Conclusions The VLSM analysis showed associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas including the thalamus that are known to cause neurologic deficits, such as aphasia or compromised vigilance, in AIS-patients with EVT. Our data suggest that higher disability, clinical impairment due to neurological deficits like aphasia, or reduced alertness of affected patients may influence the physician’s decision on using GA in EVT.

Gastrodin Attenuates Neuronal Apoptosis and Neurological Deficits after Experimental Intracerebral Hemorrhage

2020 ◽  
Vol 29 (1) ◽  
pp. 104483 ◽  
Author(s):  
Xi-chang Liu ◽  
Chang-zhu Wu ◽  
Xiao-fei Hu ◽  
Ting-ling Wang ◽  
Xiao-ping Jin ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Neuronal Apoptosis ◽  
Neurological Deficits

Hyperperfusion Syndrome: Toward a Stricter Definition

Neurosurgery ◽  
2003 ◽  
Vol 53 (5) ◽  
pp. 1053-1060 ◽  
Author(s):  
◽  
Shelagh B. Coutts ◽  
Michael D. Hill ◽  
William Y. Hu ◽  
Garnette R. Sutherland
Keyword(s):  
Carotid Artery ◽  
Intracerebral Hemorrhage ◽  
Carotid Endarterectomy ◽  
Clinical Presentation ◽  
Imaging Techniques ◽  
Neurological Deficits ◽  
Acute Hemorrhage ◽  
Motor Weakness ◽  
Hyperperfusion Syndrome ◽  
Angioplasty And Stenting

Abstract OBJECTIVE Hyperperfusion syndrome is a rare and potentially devastating complication of carotid endarterectomy or carotid artery angioplasty and stenting. With the advent of new imaging techniques, we reviewed our experience with this phenomenon. METHODS This report is a retrospective review of 129 consecutive cases of carotid endarterectomy performed between June 1, 2000, and May 31, 2002, and 44 consecutive cases of carotid artery angioplasty and stenting performed between January 1, 1997, and May 31, 2002. We specifically searched for examples of patients who developed postprocedural nonthrombotic neurological deficits that typified the hyperperfusion syndrome. RESULTS Seven cases of hyperperfusion syndrome occurred, four after endarterectomy (3.1% of carotid endarterectomy cases) and three after stenting (6.8% of stenting cases). The cases of hyperperfusion were classified as presenting with 1) acute focal edema (two cases with stroke-like presentation, attributable to edema immediately after revascularization), 2) acute hemorrhage (two cases of intracerebral hemorrhage immediately after stenting and one case immediately after endarterectomy), or 3) delayed classic presentation (two cases with seizures, focal motor weakness, and/or late intracerebral hemorrhage at least 24 hours after endarterectomy). CONCLUSION Hyperperfusion syndrome may be more common and more variable in clinical presentation than previously appreciated.

The Effect of Arteriovenous Malformation Resection on Cerebrovascular Reactivity to Carbon Dioxide

Neurosurgery ◽  
1990 ◽  
Vol 27 (2) ◽  
pp. 257-267 ◽  
Author(s):  
William L. Young ◽  
Isak Prohovnik ◽  
Isak Prohovnik ◽  
Isak Prohovnik ◽  
Eugene Ornstein ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Risk Score ◽  
Cerebrovascular Reactivity ◽  
Neurological Deficits ◽  
Control Group ◽  
Technical Problems ◽  
Before And After ◽  
Acute Increase ◽  
Patient’S History ◽  
Risk Score System

Abstract To investigate the cerebral hemodynamic changes associated with obliteration of arteriovenous malformations (AVMs), we studied 26 patients undergoing total microsurgical AVM resection during isoflurane and N2/O2anesthesia. Detectors were placed 5 to 6 cm from the margin of the lesion and in a homologous contralateral position. Cerebral blood flow (CBF) was measured using the intravenous xenon-133 technique before and after AVM resection, during both hypocapnia and normocapnia at each stage. Intraoperative changes in CBF were related to a risk score system based on the patient's history and preoperative angiograms. Seven otherwise healthy patients undergoing spinal surgery were studied to control for anesthetic effects. Patient demographic and clinical data for the AVM group conformed to the expected strata of a large AVM population. The CBF increased after excision (22 ± 1 ml/100 g/min before excision to 30 ± 2 ml/100 g/min after excision; mean ± SE. n = 25, P &lt; 0.002) without a hemispheric difference. CO2reactivity increased slightly after excision (4.2 ± 0.3% change/mm Hg before excision to 4.7 ± 0.3% change/mm Hg after excision; n = 14, P &lt; 0.02). The baseline CBF and CO2reactivity were not different from the control group. There was a weak correlation between the risk score and the percentage of change in the ipsilateral CBF, with a trend for the patients with the lowest risk to have the lowest CBF changes after resection. There was no relationship between CO2reactivity and risk grade. None of the patients awoke from anesthesia with unexpected neurological deficits. The highest CBF increases were associated with postoperative brain swelling in one patient and fatal intracerebral hemorrhage in another. Both patients had normal CO2reactivity before excision. One patient suffered postoperative intracerebral hemorrhage, attributable to technical problems, and had no increase in CBF. We conclude that, with an acute increase in the arteriovenous pressure gradient (and cerebral perfusion pressure) that results from shunt obliteration, there is an immediate global effect of AVM resection to increase CBF. Cerebrovascular reactivity to CO2remains intact both before and after excision.

scholarly journals MSC Secretome as a Promising Tool for Neuroprotection and Neuroregeneration in a Model of Intracerebral Hemorrhage

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2031
Author(s):  
Maxim Karagyaur ◽  
Stalik Dzhauari ◽  
Nataliya Basalova ◽  
Natalia Aleksandrushkina ◽  
Georgy Sagaradze ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Neurological Outcome ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Lesion Volume ◽  
Therapeutic Approaches ◽  
Beneficial Effects ◽  
Tissue Repair And Regeneration ◽  
Promising Tool ◽  
Neurologic Disorders ◽  
The Brain

Multipotent mesenchymal stromal cells (MSCs) are considered to be critical contributors to injured tissue repair and regeneration, and MSC-based therapeutic approaches have been applied to many peripheral and central neurologic disorders. It has been demonstrated that the beneficial effects of MSC are mainly mediated by the components of their secretome. In the current study, we have explored the neuroprotective potential of the MSC secretome in a rat model of intracerebral hemorrhage and shown that a 10-fold concentrated secretome of human MSC and its combination with the brain-derived neurotrophic factor (BDNF) provided a better survival and neurological outcome of rats within 14 days of intracerebral hemorrhage compared to the negative (non-treated) and positive (BDNF) control groups. We found that it was due to the ability of MSC secretome to stimulate neuron survival under conditions of glutamate-induced neurotoxicity. However, the lesion volume did not shrink in these rats, and this also correlated with prominent microglia activation. We hypothesize that this could be caused by the species-specificity of the used MSC secretome and provide evidence to confirm this. Thus, we have found that allogenic rat MSC secretome was more effective than xenogenic human MSC secretome in the rat intracerebral hemorrhage model: it reduced the volume of the lesion and promoted excellent survival and neurological outcome of the treated rats.

Neurological complications and symptom resolution following Gamma Knife surgery for brain metastases 2 cm or smaller in relation to eloquent cortices

2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 53-64 ◽  
Author(s):  
Robert E. Elliott ◽  
Stephen Rush ◽  
Amr Morsi ◽  
Nisha Mehta ◽  
Jeri Spriet ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Gamma Knife ◽  
Neurological Complications ◽  
Gamma Knife Surgery ◽  
Neurological Deterioration ◽  
Neurological Deficits ◽  
Lesion Volume ◽  
Symptom Resolution ◽  
Grade Ii ◽  
Grade Iii

Object Reports on resection of tumors in or near eloquent cortices have noted neurological complications in up to 30% of patients. This paper contains an analysis of symptom resolution and neurological morbidity following 20-Gy Gamma Knife surgery (GKS) for supratentorial brain metastases ≤ 2 cm in greatest diameter. Methods The authors performed a retrospective analysis of 98 consecutively treated adults (33 men and 65 women with a median age of 61.4 years at the time of GKS) with Karnofsky Performance Scale score ≥ 60, who underwent GKS for supratentorial brain metastases ≤ 2 cm in diameter. Lesion location was classified as noneloquent (Grade I), near eloquent (Grade II), or eloquent (Grade III), in accordance with the grading system developed by the group at M. D. Anderson Cancer Center. Following treatment, the patients underwent MR imaging and clinical examinations at 6 weeks and every 3 months thereafter. Results Ninety-eight patients underwent 20-Gy GKS for 131 metastases at initial presentation and 31 patients underwent salvage 20-Gy GKS for 76 new lesions, for a total of 207 lesions (mean lesion volume 0.44 cm3). Lesions were classified as follows: Grade I, 96 (46.4%); Grade II, 51 (24.6%); and Grade III, 60 (29%). Fifteen patients (2 with Grade II and 13 with Grade III lesions) presented with deficits referable to their lesions, yielding pre-GKS deficit rates of 7.2% per lesion and 15.3% per patient. The pre-GKS deficits improved or resolved in 10 patients (66.7%) at a median time of 2.8 months and remained stable in 3 patients (20%). Two patients (13.3%) experienced worsened neurological deficits. One patient who was neurologically intact prior to treatment developed a new hemiparesis (1 of 83 patients [1.2%]). The rates of permanent neurological deterioration following GKS for Grades I, II, and III lesions were 0% (0 of 96 tumors), 2% (1 of 51), and 3.3% (2 of 60), respectively. The pre-GKS neurological deficits and larger lesions were the most significant risk factors for post-GKS neurological deterioration. Conclusions Gamma Knife surgery performed using a 20-Gy dose provides amelioration of neurological deficits from brain metastases that are ≤ 2 cm in diameter and located in or near eloquent cortices in nearly two-thirds of patients with a low incidence of morbidity. Consistent with the surgical literature, higher rates of neurological complications were observed as proximity to eloquent regions and lesion size increased. There was no neurological deterioration in patients harboring metastases in noneloquent areas.

scholarly journals Butin attenuates brain edema in a rat model of intracerebral hemorrhage by anti inflammatory pathway

2018 ◽  
Vol 9 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Peiyu Li ◽  
Cheng Jiwu
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Treated Group ◽  
Control Group ◽  
Lesion Volume ◽  
Dependent Manner ◽  
Neurological Score ◽  
Factor Α ◽  
The Brain ◽  
Brain Tissues

Abstract Background This study evaluates the effect of butin against brain edema in intracerebral hemorrhage (ICH). Methodology ICH was induced by injecting bacterial collagenase in the brain and all the animals were separated into four groups such as control group, ICH group treated with vehicle, Butin 25 and 50 mg/kg group receives butin (25 and 50 mg/kg, i.p.)60 min after the induction of ICH in all animals. One day after neurological score, hemorrhagic injury and expressions of protein responsible for apoptosis and inflammatory cytokines were assessed in the brain tissue of ICH rats. Result Neurological scoring significantly increased and hemorrhagic lesion volume decreased in butin treated group of rats compared to ICH group. However, treatment with butin significantly decreases the ratio of Bax/Bcl-2 and protein expression of Cleaved caspase-3 than ICH group in dose dependent manner. Level of inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) in the brain tissues were significantly decreased in the butin treated group than ICH group. In addition butin attenuates the altered signaling pathway of NF-κB in the brain tissues of ICH rats. Conclusion Our study concludes that butin attenuates the altered behavior and neuronal condition in ICH rats by reducing apoptosis and inflammatory response.

Abstract TP376: Heme Oxygenase-1 is Essential for Hematoma Clearance After Intracerebral Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Liyan Zhang ◽  
Xiurong Zhao ◽  
Guanghua Sun ◽  
Jaroslaw Aronowski
Keyword(s):  
Intracerebral Hemorrhage ◽  
Rat Brain ◽  
Heme Oxygenase ◽  
Functional Recovery ◽  
Protoporphyrin Ix ◽  
Neuronal Injury ◽  
Neurological Deficits ◽  
Sublethal Dose ◽  
Heme Oxygenase 1 ◽  
Secondary Brain Injury

Background: After intracerebral hemorrhage (ICH), the red blood cells (RBC) and their hemolytic products within brain hematoma trigger adverse biochemical events, leading to secondary brain injury and neurological deficits. Thus, efficient removal of hematoma components is essential for achieving inflammation resolution and functional recovery. The inducible heme-oxygenase (HO-1) is a key rate-limiting enzyme that catabolizes heme into iron, CO, and biliverdin. The present study investigated the role of HO-1 in microglia/macrophages (MΦ)-mediated phagocytosis of RBC; and also assessed the spatial and temporal expression of HO-1 in ICH-affected brain, as well as its possible role in the clearance of hematoma components following ICH modeled in rodents. Methods and Results: First, we employed the rat brain MΦ. Upon exposing to RBC, MΦ phagocytize RBC; and HO-1 was induced during this process. Co-incubating tin-protoporphyrin IX (SnPP, a competitive HO-1 inhibitor) with RBC significantly delayed RBC internalization by MΦ. Removal of SnPP from the culture medium led to a rapid recovery of MΦ’s phagocytic function, suggesting that SnPP-induced inhibition is a reversible process. Subjecting neuron-microglia co-cultures to RBC plus sublethal dose of oxygen-deprivation (an ICH-like insult) triggered neuronal injury, as assessed using neurofilament degradation assay and loss of NeuN-positive cells; and addition of SnPP further aggravated the neuronal injury. Additional studies showed that after ICH, HO-1 is up-regulated in hematoma-affected rat brain tissues starting from 6h, reaching the maximum level at 3-7days, and persisting for at least 10 days after ICH. Double immunohistochemistry of HO-1 and brain cell markers shows that the most HO-1-positive cells are Iba1-positive MΦ. Administration of SnPP for 7 days, (7.5 mg/kg, ip, twice a day) delayed hematoma clearance by 27.8% and significantly impaired the functional recovery, as measured 7 days after ICH. Histological analyses showed that there are more TUNEL-positive neurons in the hematoma-affected brain tissue in SnPP-treated mouse brains. Conclusion: Our study suggests that HO-1 is essential for phagocytosis of RBC by MΦ, which is critical for endogenous clearance of hematoma after ICH.

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