Functional assessments in the rodent stroke model

Schaar, Krystal; Brenneman, Miranda M.; Savitz, Sean I

doi:10.1186/2040-7378-2-13

Cited by 453 publications

(352 citation statements)

References 48 publications

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“…The corner test assesses sensory and motor asymmetries after ischemic injuries (17)(18)(19). The corner apparatus consists of two wooden boards (30 cm × 20 cm × 1 cm) that are attached to each other at a 30°angle.…”

Section: Methodsmentioning

confidence: 99%

“…Both tests are frequently used in ischemic injury models: The corner test is used to assess sensory and motor asymmetries (17)(18)(19), whereas the pole test is used to examine motor dysfunction (19,20). In the corner test, ET-1 injection with PBS to the right internal capsule resulted in a slight preference to turn right (Fig.…”

Section: Endothelin-1 Injection Induces Cytosolic Translocation Of Hmmentioning

confidence: 99%

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High-mobility group box-1 as an autocrine trophic factor in white matter stroke

Choi

Cui

Chowdhury

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Maintenance of white matter integrity in health and disease is critical for a variety of neural functions. Ischemic stroke in the white matter frequently results in degeneration of oligodendrocytes (OLs) and myelin. Previously, we found that toll-like receptor 2 (TLR2) expressed in OLs provides cell-autonomous protective effects on ischemic OL death and demyelination in white matter stroke. Here, we identified high-mobility group box-1 (HMGB1) as an endogenous TLR2 ligand that promotes survival of OLs under ischemic stress. HMGB1 rapidly accumulated in the culture medium of OLs exposed to oxygen-glucose deprivation (OGD). This conditioned medium exhibited a protective activity against ischemic OL death that was completely abolished by immunodepletion of HMGB1. Knockdown of HMGB1 or application of glycyrrhizin, a specific HMGB1 inhibitor, aggravated OGD-induced OL death, and recombinant HMGB1 application reduced the extent of OL death in a TLR2-dependent manner. We confirmed that cytosolic translocation of HMGB1 and activation of TLR2-mediated signaling pathways occurred in a focal white matter stroke model induced by endothelin-1 injection. Animals with glycyrrhizin coinjection showed an expansion of the demyelinating lesion in a TLR2-dependent manner, accompanied by aggravation of sensorimotor behavioral deficits. These results indicate that HMGB1/ TLR2 activates an autocrine trophic signaling pathways in OLs and myelin to maintain structural and functional integrity of the white matter under ischemic conditions. white matter stroke | oligodendrocyte | toll-like receptor 2 | HMGB1 | myelination W hite matter in the vertebrate brain is characterized by the presence of myelinated axonal fibers and glial cells, predominantly myelin-producing oligodendrocytes (OLs) (1). The myelin sheath enables rapid communication of neural signals at a millisecond timescale between different parts of the cerebral cortex or different regions of the CNS (2). Therefore, maintaining the integrity of white matter in health and disease, especially of OLs and the myelin sheath, is critical to the performance of a variety of brain functions. Furthermore, recent studies have shown that myelination and OL generation in adulthood are actively regulated in response to neural activities (3, 4), highlighting the potential contribution of white matter plasticity to learning and higher cognitive functions.Ischemic stroke that occurs in the white matter often results in degeneration of OLs and demyelination (5, 6). Consequently, patients with white matter stroke suffer from a wide range of neurological dysfunctions. For example, focal ischemic stroke in the internal capsule may result in severe hemiparesis (7). Furthermore, both cognitive deficits and gait disturbance are hallmarks of Binswanger's subcortical vascular dementia that is the most severe form of white matter stroke (8). How ischemia leads to OL degeneration and demyelination is poorly understood. We previously reported that toll-like receptor 2 (TLR2) expressed in OLs plays a protect...

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Section: Methodsmentioning

confidence: 99%

Section: Endothelin-1 Injection Induces Cytosolic Translocation Of Hmmentioning

confidence: 99%

High-mobility group box-1 as an autocrine trophic factor in white matter stroke

Choi

Cui

Chowdhury

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…A grading scale of 0 to 8 is used to assess behavioral deficits after cerebral damage. 27 Zero value represents an animal without neurologic deficit and 8 represents an animal with high neurologic deficit.…”

Section: Behavioral Testsmentioning

confidence: 99%

Blood Glutamate Grabbing Does Not Reduce the Hematoma in an Intracerebral Hemorrhage Model but it is a Safe Excitotoxic Treatment Modality

Silva‐Candal

Vieites‐Prado

Gutiérrez-Fernández

et al. 2015

J Cereb Blood Flow Metab

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Recent studies have shown that blood glutamate grabbing is an effective strategy to reduce the excitotoxic effect of extracellular glutamate released during ischemic brain injury. The purpose of the study was to investigate the effect of two of the most efficient blood glutamate grabbers (oxaloacetate and recombinant glutamate oxaloacetate transaminase 1: rGOT1) in a rat model of intracerebral hemorrhage (ICH). Intracerebral hemorrhage was produced by injecting collagenase into the basal ganglia. Three treatment groups were developed: a control group treated with saline, a group treated with oxaloacetate, and a final group treated with human rGOT1. Treatments were given 1 hour after hemorrhage. Hematoma volume (analyzed by magnetic resonance imaging (MRI)), neurologic deficit, and blood glutamate and GOT levels were quantified over a period of 14 days after surgery. The results observed showed that the treatments used induced a significant reduction of blood glutamate levels; however, they did not reduce the hematoma, nor did they improve the neurologic deficit. In the present experimental study, we have shown that this novel therapeutic strategy is not effective in case of ICH pathology. More importantly, these findings suggest that blood glutamate grabbers are a safe treatment modality that can be given in cases of suspected ischemic stroke without previous neuroimaging. Keywords: blood glutamate grabbing; GOT; intracerebral hemorrhage; oxaloacetate; protection INTRODUCTION Intracerebral hemorrhage (ICH) represents approximately 15% of all strokes; moreover, the incidence of ICH is expected to grow, given the increase in the use of anticoagulants and aging of the population. Journal of Cerebral Blood1 It is a type of acute stroke characterized by extravasation of blood into the brain parenchyma and formation of hematoma. Hematoma produces primary damage because of the toxic effect of thrombin, a mass effect due to the extravasated blood that compresses the surrounding brain tissue; sometimes, this damage is also enhanced by rebleeding. Primary damage is followed by a secondary damage mainly characterized by edema formation, tissular ischemia, and glutamate excitotoxicity.

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“…It is important to note that the improved behavioral recovery in multiparous females may simply reflect the smaller infarct seen in these mice rather than an enhanced delayed angiogenic response. Behavioral deficits and recovery are known to be related to the location and severity of the initial stroke injury (30,31). However, the near complete preservation of sensorimotor and cognitive function in the multiparous mice is nonetheless impressive, given that the striatal infarct was prominent in both groups.…”

Section: Discussionmentioning

confidence: 96%

Multiparity improves outcomes after cerebral ischemia in female mice despite features of increased metabovascular risk

Ritzel

Patel

Spychala

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Females show a varying degree of ischemic sensitivity throughout their lifespan, which is not fully explained by hormonal or genetic factors. Epidemiological data suggest that sex-specific life experiences such as pregnancy increase stroke risk. This work evaluated the role of parity on stroke outcome. Age-matched virgin (i.e., nulliparous) and multiparous mice were subjected to 60 min of reversible middle cerebral artery occlusion and evaluated for infarct volume, behavioral recovery, and inflammation. Using an established mating paradigm, fetal microchimeric cells present in maternal mice were also tracked after parturition and stroke. Parity was associated with sedentary behavior, weight gain, and higher triglyceride and cholesterol levels. The multiparous brain exhibited features of immune suppression, with dampened baseline microglial activity. After acute stroke, multiparous mice had smaller infarcts, less glial activation, and less behavioral impairment in the critical recovery window of 72 h. Behavioral recovery was significantly better in multiparous females compared with nulliparous mice 1 mo after stroke. This recovery was accompanied by an increase in poststroke angiogenesis that was correlated with improved performance on sensorimotor and cognitive tests. Multiparous mice had higher levels of VEGF, both at baseline and after stroke. GFP + fetal cells were detected in the blood and migrated to areas of tissue injury where they adopted endothelial morphology 30 d after injury. Reproductive experience has profound and complex effects on neurovascular health and disease. Inclusion of female mice with reproductive experience in preclinical studies may better reflect the life-long patterning of ischemic stroke risk in women.sex differences | multiparity | microglia | ischemic stroke | microchimerism N early 800,000 people in the United States experience a new or recurrent stroke each year, and 55,000 more women than men are affected by stroke (1). Stroke is a sexually dimorphic disease impacted by genetics, hormones, and the environment (2). According to CDC data, 85% of women in the United States have given birth by age 40, whereas the number of lifetime pregnancies per woman varies by race and socioeconomic status. Therefore, child-bearing women represent a significant proportion of the female population, including those at risk for stroke. Moreover, this suggests that a large proportion of the elderly female populationwho is at highest risk for stroke-may be differentially at risk. Epidemiological data suggest that increasing parity is associated with higher risk of cardiovascular disease (CVD) and stroke and late-life vascular comorbidities, including carotid atherosclerosis (3, 4). However, recent reports suggest that parity has a significant protective effect against CVD mortality (5). The effect of parity on outcome following ischemic stroke is yet unresolved.Pregnancy induces profound acute and long-term physiological changes in the body that influence future vascular health through hormonally med...

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Functional assessments in the rodent stroke model

Cited by 453 publications

References 48 publications

High-mobility group box-1 as an autocrine trophic factor in white matter stroke

High-mobility group box-1 as an autocrine trophic factor in white matter stroke

Blood Glutamate Grabbing Does Not Reduce the Hematoma in an Intracerebral Hemorrhage Model but it is a Safe Excitotoxic Treatment Modality

Multiparity improves outcomes after cerebral ischemia in female mice despite features of increased metabovascular risk

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