endothelin-1 and Intracranial-Hemorrhages

Stroke, broadly subdivided into ischemic and hemorrhagic subtypes, is a serious health-care problem worldwide. Previous studies have suggested ischemic and hemorrhagic stroke could present different functional recovery patterns. However, little attention has been given to this neurobiological finding. Coincidently, astrocyte morphology could be related to improved sensorimotor recovery after skilled reaching training and modulated by physical exercise and environmental enrichment. Therefore, it is possible that astrocyte morphology might be linked to differential recovery patterns between ischemic and hemorrhagic stroke. Thus, we decided to compare long-term GFAP-positive astrocyte morphology after ischemic (IS, n=5), hemorrhagic (HS, n=5) and sham (S, n=5) stroke groups (induced by endothelin-1, collagenase type IV-S and salina, respectively). Our results showed ischemic and hemorrhagic stroke subtypes induced similar long-term GFAP-positive astrocyte plasticity (P>0.05) for all evaluated measures (regional and cellular optical density; astrocytic primary processes ramification and length; density of GFAP positive astrocytes) in perilesional sensorimotor cortex and striatum. These interesting negative results discourage similar studies focused on long-term plasticity of GFAP-positive astrocyte morphology and recovery comparison of stroke subtypes.

Topics: Animals; Astrocytes; Collagenases; Corpus Striatum; Endothelin-1; Glial Fibrillary Acidic Protein; Intracranial Hemorrhages; Ischemia; Prognosis; Rats; Rats, Wistar; Sensorimotor Cortex; Stroke

Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults.

Topics: Animals; Brain; Brain Ischemia; Collagenases; Endothelin-1; Intracranial Hemorrhages; Male; Microinjections; Motor Activity; Motor Skills; Rats; Recovery of Function; Stroke

To observe the effects of minimally invasive procedures for the evacuation of intracerebral hematomas on perihematomal ET-1 expression and their correlation with blood-brain barrier (BBB) permeability. Forty-five rabbits (2.8-3.4 kg body weight) were randomly divided into a normal control group (NC group, 15 rabbits), a model control group (MC group, 15 rabbits) and a minimally invasive group (MI group, 15 rabbits). A model of intracerebral hemorrhage (ICH) was prepared in the MC and MI groups by infusing autologous arterial blood into the rabbits' brains; the same procedure was also performed in the NC group but without infusing blood into the rabbits' brains. The intracerebral hematomas were evacuated by a stereotactic procedure in the minimally invasive group 6 h after the model was established. The neurological functions, ET-1 expression and the perihematomal BBB permeability were determined and analyzed in all of the animals. The number of endothelial cells with ET-1-positive expression and the perihematomal BBB permeability significantly increased 1, 3, and 7 days after the ICH model was prepared successfully, as compared to the NC group. In the MI group, however, both measurements decreased markedly compared with the MC group at the same time point. A positive correlation between the number of endothelial cells with ET-1-positive expression and BBB permeability was observed. Increased BBB permeability might be associated with perihematomal ET-1 levels. Minimally invasive procedures for the evacuation of intracerebral hematomas could significantly decrease BBB permeability in perihematomal brain tissues, likely by reducing the production of ET-1.

Topics: Animals; Blood-Brain Barrier; Brain; Disease Models, Animal; Drainage; Endothelin-1; Female; Immunohistochemistry; Intracranial Hemorrhages; Male; Minimally Invasive Surgical Procedures; Nervous System Diseases; Neurosurgical Procedures; Permeability; Rabbits; Stereotaxic Techniques; Tomography, X-Ray Computed

Concentrations of plasma vascular tone regulation markers that are indicators of endothelium dysfunction in the acute phase of ischemic stroke and their effect on the development of hemorrhagic transformation (HT) of the lesion focus have been studied. Concentrations of renin, endothelin 1-21, neuron-specific enolase, NT-proCNP, soluble adhesion molecules (sICAM) were measured in 67 patients on days 1, 3-4. Significantly higher concentrations of renin, endothelin 1-21, neuron-specific enolase were found in patients with HT in the first day compared to patients without HT. The level of NT-proCNP was lower in patients with HT; the increase in the severity of hemorrhagic component led to the elevation of neuron-specific enolase and sICAM concentrations. In conclusion, both markers of blood-brain barrier damage and regulating factors of vascular tone may play a predictive role in the development of HT in ischemic stroke.

Topics: Aged; Biomarkers; Blood-Brain Barrier; Cell Adhesion Molecules; Endothelin-1; Endothelium, Vascular; Female; Humans; Intracranial Hemorrhages; Male; Natriuretic Peptide, C-Type; Phosphopyruvate Hydratase; Renin; Stroke