Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway

Purpose: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. Methods: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nickend labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. Results: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Conclusion: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Taurine promotes axonal sprouting via Shh-mediated mitochondrial improvement in stroke

Purpose: Motor function is restored by axonal sprouting in ischemic stroke. Mitochondria play a crucial role in axonal sprouting. Taurine (TAU) is known to protect the brain against experimental stroke, but its role in axonal sprouting and the underlying mechanism are unclear. Methods: We evaluated the motor function of stroke mice using the rotarod test on days 7, 14, and 28. Immunocytochemistry with biotinylated dextran amine was used to detect axonal sprouting. We observed neurite outgrowth and cell apoptosis in cortical neurons under oxygen and glucose deprivation (OGD), respectively. Furthermore, we evaluated the mitochondrial function, adenosine triphosphate (ATP), mitochondrial DNA (mtDNA), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG-1α), transcription factor A of mitochondria (TFAM), protein patched homolog 1 (PTCH1), and cellular myelocytomatosis oncogene (c-Myc). Results: TAU recovered the motor function and promoted axonal sprouting in ischemic mice. TAU restored the neuritogenesis ability of cortical neurons and reduced OGD-induced cell apoptosis. TAU also reduced reactive oxygen species, stabilized mitochondrial membrane potential, enhanced ATP and mtDNA content, increased the levels of PGC-1α, and TFAM, and restored the impaired levels of PTCH1, and c-Myc. Furthermore, these TAU-related effects could be blocked using an Shh inhibitor (cyclopamine). Conclusion: Taurine promoted axonal sprouting via Shh-mediated mitochondrial improvement in ischemic stroke.

Tratamento de reação inflamatória cerebral após Acidente Vascular Encefálico (AVE) e Trauma Cranioencefálico (TCE) em cão / Treatment of inflammatory brain reaction after Brain Vascular Accident (CVA) and Traumatic Brain Injury (TBI) in a dog / Tratamiento de la reacción inflamatoria cerebral después de un Accidente Vascular Cerebral (ACV) y Traumatismo Cerebral (TEC) en un perro

O presente relato de caso tem por objetivo descrever a ocorrência de quadro neurológico tardio, pós-trauma cranioencefálico em um paciente canino, atendido em clínica veterinária particular. O animal foi avaliado clinicamente, com alterações neurológicas intensas de ataxia vestibular, andar compulsivo, paresia, perda de propriocepção nos quatro membros, miose bilateral, anisocoria, entre outros. O diagnóstico foi presuntivo, auxiliado por ressonância magnética, e baseado no histórico detalhado. O tratamento clínico foi determinado empiricamente, a base de dexametasona comercial, associada a metionina, nicotinamida e piridoxina. O paciente apresentou melhora clínica rápida, diminuindo inflamação encefálica e desaparecimento de quadro neurológico.

The present case report aims to describe the occurrence of a late neurological condition, after traumatic brain injury in a canine patient, treated at a private veterinary clinic. The animal was clinically evaluated, with severe neurological alterations of vestibular ataxia, compulsive gait, paresis, loss of proprioception in all four limbs, bilateral miosis, anisocoria, among others. Diagnosis was presumptive, aided by MRI, and based on detailed history. Clinical treatment was empirically determined, based on commercial dexamethasone, associated with methionine, nicotinamide and pyridoxine. The patient showed rapid clinical improvement, with no neurological picture.

El presente reporte de caso tiene como objetivo describir la aparición de una condición neurológica tardía, posterior a un traumatismo craneoencefálico en un paciente canino, atendido en una clínica veterinaria privada. El animal fue evaluado clínicamente, con alteraciones neurológicas severas de ataxia vestibular, marcha compulsiva, paresia, pérdida de propiocepción en las cuatro extremidades, miosis bilateral, anisocoria, entre otras. El diagnóstico fue presuntivo, ayudado por resonancia magnética y basado en una historia clínica detallada. El tratamiento clínico se determinó empíricamente, a base de dexametasona comercial, asociada a metionina, nicotinamida y piridoxina. El paciente presentó una rápida mejoría clínica sin cuadro neurológico.

Hemorrhagic stroke in a dog with anaplastic carcinoma of the mammary gland

Background: Anaplastic carcinoma of the mammary gland is considered a highly invasive and malignant neoplasia, whichusually leads to neoplastic thrombosis and epidermal ulceration due to invasiveness of lymphatic vessels by tumor emboli.Loss of epidermal barrier predisposes to secondary bacterial infection, mainly by commensal bacteria of the skin, andsepticemia can be observed in cases of systemic dissemination. Neoplastic emboli and septic thrombi can lead to vascularobstruction, which can predispose to infarction in multiple organs. The aim of this case report is to describe a case ofhemorrhagic stroke in a dog with anaplastic carcinoma of the mammary gland.Case: A 12-year-old, mixed breed, female spayed canine presented with mammary tumor with plaque formation, associatedwith skin ulceration which extended to the medial region of pelvic limbs. The animal also displayed neurologic clinicalsigns characterized by stupor, opisthotonos and apathy. Due to poor prognosis, the canine was euthanized and submittedto necropsy. During external examination, the animal was in a good body condition, had moderately pale mucosae, andit was noted a nodular plaque in the abdominal ventral area extending from thoracic to inguinal mammary gland. Themass was firm and white, extensively ulcerated, and extending from the thoracic to inguinal mammary gland. There wasa well circumscribed area of infarction in the spleen and kidney. In the cerebral cortex it was observed an extensive areaof hemorrhage with adhered blood clot from frontal to temporal lobe. There were multiple well circumscribed, firm, andwhite areas in the myocardium. Histologically, the neoplastic proliferation was composed by epithelial cells with high pleomorphism, features of malignancy, and no delimitations, leading to the diagnosis of anaplastic carcinoma of the mammarygland. Admixed with tumor cells there were multiple areas of hemorrhage, necrosis and thrombosis...

Hemorrhagic stroke in a dog with anaplastic carcinoma of the mammary gland

Background: Anaplastic carcinoma of the mammary gland is considered a highly invasive and malignant neoplasia, whichusually leads to neoplastic thrombosis and epidermal ulceration due to invasiveness of lymphatic vessels by tumor emboli.Loss of epidermal barrier predisposes to secondary bacterial infection, mainly by commensal bacteria of the skin, andsepticemia can be observed in cases of systemic dissemination. Neoplastic emboli and septic thrombi can lead to vascularobstruction, which can predispose to infarction in multiple organs. The aim of this case report is to describe a case ofhemorrhagic stroke in a dog with anaplastic carcinoma of the mammary gland.Case: A 12-year-old, mixed breed, female spayed canine presented with mammary tumor with plaque formation, associatedwith skin ulceration which extended to the medial region of pelvic limbs. The animal also displayed neurologic clinicalsigns characterized by stupor, opisthotonos and apathy. Due to poor prognosis, the canine was euthanized and submittedto necropsy. During external examination, the animal was in a good body condition, had moderately pale mucosae, andit was noted a nodular plaque in the abdominal ventral area extending from thoracic to inguinal mammary gland. Themass was firm and white, extensively ulcerated, and extending from the thoracic to inguinal mammary gland. There wasa well circumscribed area of infarction in the spleen and kidney. In the cerebral cortex it was observed an extensive areaof hemorrhage with adhered blood clot from frontal to temporal lobe. There were multiple well circumscribed, firm, andwhite areas in the myocardium. Histologically, the neoplastic proliferation was composed by epithelial cells with high pleomorphism, features of malignancy, and no delimitations, leading to the diagnosis of anaplastic carcinoma of the mammarygland. Admixed with tumor cells there were multiple areas of hemorrhage, necrosis and thrombosis...(AU)

Metastatic osteosarcoma as a cause of hemorrhagic stroke in a dog

The aim of this case report is to describe an uncommon hemorrhagic cerebrovascular accident (CVA) associated with an osteosarcoma (OSA) metastasis. Cerebrovascular accident (CVA) is the acute onset of a neurological deficit from any change in blood supply resulting from a pathological process, characterizing a stroke and among all the causes, the neoplastic thrombus of osteosarcoma, specifically, is the most infrequent in clinical practice. A seven-year-old female midsize mixed-breed dog was submitted to a forelimb amputation for showing an osteoblastic OSA in proximal humerus. Three weeks later, the patient presented uninterruptible seizure and coma, resulting in death. At necropsy, it was observed afriable and reddish mass in the left frontal cortex which, microscopically was constituted by OSA metastasis in association with multiple ruptures of blood vessels and focally extensive severe bleeding, which caused a CVA. At immunohistochemistry, neoplastic cells of the humerus and the brain metastasis were positive for vimentin and osteonectin, confirming the diagnosis of osteoblastic OSA. The reports about OSA metastasis on the brain are rare in animals and humans, what could be related to the low frequency and few diagnosis ante and post-mortem. As uncommon as the description of OSA metastasis to the brain, is the CVA associated to them, demonstrating that reporting cases related to these clinical and anatomopathological lesions are important for the scientific community.(AU)

Metastatic osteosarcoma as a cause of hemorrhagic stroke in a dog

The aim of this case report is to describe an uncommon hemorrhagic cerebrovascular accident (CVA) associated with an osteosarcoma (OSA) metastasis. Cerebrovascular accident (CVA) is the acute onset of a neurological deficit from any change in blood supply resulting from a pathological process, characterizing a stroke and among all the causes, the neoplastic thrombus of osteosarcoma, specifically, is the most infrequent in clinical practice. A seven-year-old female midsize mixed-breed dog was submitted to a forelimb amputation for showing an osteoblastic OSA in proximal humerus. Three weeks later, the patient presented uninterruptible seizure and coma, resulting in death. At necropsy, it was observed afriable and reddish mass in the left frontal cortex which, microscopically was constituted by OSA metastasis in association with multiple ruptures of blood vessels and focally extensive severe bleeding, which caused a CVA. At immunohistochemistry, neoplastic cells of the humerus and the brain metastasis were positive for vimentin and osteonectin, confirming the diagnosis of osteoblastic OSA. The reports about OSA metastasis on the brain are rare in animals and humans, what could be related to the low frequency and few diagnosis ante and post-mortem. As uncommon as the description of OSA metastasis to the brain, is the CVA associated to them, demonstrating that reporting cases related to these clinical and anatomopathological lesions are important for the scientific community.

Hemorrhagic stroke in children caused by Bothrops marajoensis envenoming: a case report

According to the World Health Organization, snakebites are considered neglected diseases. Bothrops, the genus most frequently implicated in envenomations in Brazil, includes the species B. marajoensis Hoge, 1966, part of the complex B. atrox, which is found in the savannas of Marajó Island, Pará state, Brazil, a region that presents scarce epidemiological data. This work reports the first case of hemorrhagic stroke in a child, attributed to delayed medical care after snakebite envenoming by Bothrops marajoensis in Anajás city, Marajó Island, Pará, Brazil, which led to permanent hemiplegia as a sequela.(AU)

Hemorrhagic stroke in children caused by Bothrops marajoensis envenoming: a case report

According to the World Health Organization, snakebites are considered neglected diseases. Bothrops, the genus most frequently implicated in envenomations in Brazil, includes the species B. marajoensis Hoge, 1966, part of the complex B. atrox, which is found in the savannas of Marajó Island, Pará state, Brazil, a region that presents scarce epidemiological data. This work reports the first case of hemorrhagic stroke in a child, attributed to delayed medical care after snakebite envenoming by Bothrops marajoensis in Anajás city, Marajó Island, Pará, Brazil, which led to permanent hemiplegia as a sequela.(AU)

Hemorrhagic stroke in children caused by Bothrops marajoensis envenoming: a case report

According to the World Health Organization, snakebites are considered neglected diseases. Bothrops, the genus most frequently implicated in envenomations in Brazil, includes the species B. marajoensis Hoge, 1966, part of the complex B. atrox, which is found in the savannas of Marajó Island, Pará state, Brazil, a region that presents scarce epidemiological data. This work reports the first case of hemorrhagic stroke in a child, attributed to delayed medical care after snakebite envenoming by Bothrops marajoensis in Anajás city, Marajó Island, Pará, Brazil, which led to permanent hemiplegia as a sequela.

Small breed dogs with confirmed stroke: concurrent diseases and sonographic findings / Acidente vascular cerebral em cães de raças pequenas: achados sonográficos e doenças concomitantes

Cerebrovascular accidents (CVA) are important causes of neurological clinical signs in dogs. The objective of this work was to describe concurrent diseases and ultrasonographic features in dogs with CVA confirmed through postmortem evaluation. All medical records of transcranial Doppler ultrasonography (TCDUS) examinations performed in 512 dogs between 2007 and 2009 were reviewed, searching for history and clinical diagnosis, as well as sonographic and histological results. Forty-two dogs were selected, showing acute onset of clinical signs with no progressive focal cerebral dysfunction and diagnosis of cerebrovascular disease confirmed at necropsy. Concurrent diseases and conditions were: cerebral amyloid microangiopathy (33%), endocrinopathies (31%), coagulopathy (24%), Schnauzer hyperlipemia (7%) and unknown (5%). The relation between sonography and histology results indicated 100% sensitivity and 90% specificity for focal lesion detection. A diffuse decrease in echogenicity was related to inflammatory diseases and/or edema with 62% sensitivity. A diffuse increase in echogenicity has 100% sensitivity and was usually related to aging changes. This study showed the occurrence of coexisting diseases with CVA and sonographic features of these conditions in small breed dogs.(AU)

O diagnóstico de acidente vascular cerebral (AVC) em cães é considerado importante causa de sinais clínicos neurológicos. Este trabalho objetivou descrever as doenças concomitantes e os aspectos sonográficos em cães com AVC confirmados por meio da avaliação post-mortem. Foram revisados os exames de ultrassonografia Doppler transcraniana (USDTC) realizados em 512 cães entre os anos de 2007 e 2009, pesquisando-se o histórico e o diagnóstico clínico, assim como os achados ultrassonográficos e histológicos. Destes, foram selecionados 42 cães que apresentavam sinais clínicos agudos de alteração cerebral focal não progressiva, e o diagnóstico de AVC foi confirmado na necropsia. As doenças e as condições clínicas concomitantes foram: microangiopatia amiloide cerebral (33%), endocrinopatias (31%), coagulopatias (24%), hiperlipemia do Schnauzer (7%) e inconclusivo (5%). Relacionando-se os resultados ultrassonográficos e histológicos, observaram-se 100% de sensibilidade e 90% de especificidade para a detecção de lesões focais. O diagnóstico de diminuição difusa da ecogenicidade foi relacionado a processos inflamatórios e/ou edema com 62% de sensibilidade. O diagnóstico de aumento difuso da ecogenicidade apresentou 100% de sensibilidade e estava geralmente relacionado a alterações senis. Este estudo demonstrou a ocorrência de doenças coexistentes com o AVC e os aspectos ultrassonográficos destas condições em cães de raças pequenas.(AU)