RESUMO
Ischemic stroke represents a major cause of adult death and severe neurological disability worldwide. Reperfusion following brain ischemia produces an inflammatory cascade that increases brain damage. In this context, matrix metalloproteinases (MMPs) play an important role as pro-inflammatory mediators. The MMP 2 up-regulation seems to promote matrix degradation, blood-brain barrier (BBB) disruption and facilitates the influx of peripheral inflammatory cells to the brain after stroke. However, there are not studies about MMP-1 in this condition. The aim of this study is to evaluate the association of brain damage, inflammatory response and the immunostaining profile of matrix metalloproteinases 1 and 2 after transient global cerebral ischemia. Mice were submitted to bilateral common carotid arterial occlusion (BCCAo) during 25 min. After three days of reperfusion, the neurological deficit score was evaluated and the animals were euthanized. Brain samples were collected in order to analyze the histopathological damage, MMPs 1 and 2 immunostaining and cytokines and chemokines levels. Ischemic group showed neurological deficits associated with brain lesions, characterized by necrotic core and penumbra zone three days after reperfusion. Higher brain immunostaining of MMP-1 and MMP-2 was observed in BCCAo samples than in sham samples. Ischemic group also exhibited increased brain levels of the cytokines tumoral necrosis factor (TNF) and interleukin 1ß (IL-1ß), chemokine (C-X-C motif) ligand 1 (CXCL1), and chemokine (C-C motif) ligand 5 (CCL5) in comparison to sham group. Our results suggest that the MMP-1 and MMP-2 raise, associated with the up-regulation of inflammatory mediators, contributes to brain damage and neurological deficits after global brain ischemia followed by three days of reperfusion in mice.
Assuntos
Encéfalo/enzimologia , Citocinas/metabolismo , Ataque Isquêmico Transitório/enzimologia , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Quimiocina CCL5/metabolismo , Quimiocina CXCL1/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Ataque Isquêmico Transitório/patologia , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Necrose , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Regulação para CimaRESUMO
It has been widely recognized that the hippocampus and striatum are clearly more susceptible to oxidative stress than the remaining brain regions. However, the mechanism involved is not known. The activities of the antioxidant enzymes CuZn-superoxide dismutase (SOD), Mn-SOD and catalase were measured in the hippocampus and striatum and the results were compared to cortex and cerebellum (less susceptible to oxidative stress) after 3 h of a global transient ischemia/reperfusion. CuZn-SOD activities were reduced in all brain regions, but mainly in the hippocampus and striatum. Mn-SOD activity was lowered in the striatum, whereas catalase activity was reduced in the hippocampus and striatum. Our findings indicate that in the earlier phase of ischemia/reperfusion the decay in activities of catalase and SOD may be related with the high susceptibility of the hippocampus and striatum to oxidative damage.
Assuntos
Encéfalo/enzimologia , Catalase/metabolismo , Ataque Isquêmico Transitório/enzimologia , Traumatismo por Reperfusão/enzimologia , Superóxido Dismutase/metabolismo , Animais , Masculino , Ratos , Ratos WistarRESUMO
The idiopathic stabbing headache (ISH) is characterized by a stabbing pain of short duration, variable localization and an errant evolution pattern. As its biological mechanisms are unknown and the treatment options are little effective, this disorder shows a strong impact on the patient's life. Two females and one male, aged 76, 66 and 72 years, respectively, started presenting ISH within 20 days after the onset of a stroke. All the patients were treated for the ISH with celecoxib, a COX-2 specific inhibitor, with full recovery from ISH up to 6 days after it was first administered. The interruption of the drug 60 days after the treatment with celecoxib induced again the appearance of algic symptoms in two patients. We concluded that cerebrovascular diseases (CD) can lead to ISH and that the COX-2 inhibitor can be an effective prophylactic drug for ISH after CD.
Assuntos
Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Cefaleia/tratamento farmacológico , Cefaleia/etiologia , Isoenzimas/antagonistas & inibidores , Sulfonamidas/uso terapêutico , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/enzimologia , Celecoxib , Transtornos Cerebrovasculares/enzimologia , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Feminino , Cefaleia/enzimologia , Humanos , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/enzimologia , Isoenzimas/metabolismo , Masculino , Proteínas de Membrana , Paresia/complicações , Paresia/tratamento farmacológico , Paresia/enzimologia , Prostaglandina-Endoperóxido Sintases/metabolismo , PirazóisRESUMO
Cerebral ischemia causes cell death of vulnerable neurons in mammalian brain. Wistar adult rats (male and female, weighing 180-280 g) were submitted to 2 min, 10 min, or to 2 and 10 min (separated by a 24-h interval) of transient forebrain ischemia by the four-vessel occlusion method. Animals subjected to the longer ischemic episodes had massive necrosis of pyramidal CA1 cells of the hippocampus, while animals receiving double ischemia (2 + 10 min) showed neuronal tolerance to the ischemic insult. ATP-diphosphohydrolase activity from hippocampal synaptosomes was assayed in these three groups (N = 6 animals/group) under two conditions: no reperfusion and 5-min of reperfusion. The control values for ATPase and ADPase activities were 144.7 +/- 18.8 and 60.6 +/- 5.24 nmol Pi min-1 mg protein-1, respectively. The 10-min group without reperfusion showed an enhancement of approximately 20% for ATPase and ADPase activities. In reperfused rats, only the 2-min group had a 20% increase in both enzymatic activities. We suggest that modulation of ATP-diphosphohydrolase activity might be involved in molecular events that follow both ischemia and reperfusion.
Assuntos
Apirase/metabolismo , Hipocampo/enzimologia , Ataque Isquêmico Transitório/enzimologia , Sinaptossomos/enzimologia , Adenosina Trifosfatases/metabolismo , Animais , Feminino , Masculino , Ratos , Ratos Wistar , Reperfusão , Fatores de TempoRESUMO
Cerebral ischemia causes cell death of vulnerable neurons in mammalian brain. Wistar adult rats (male and female, weighing 180-280 g) were submitted to 2 min, 10 min, or to 2 and 10 min (separated by a 24-h interval) of transient forebrain ischemia by the four-vessel occlusion method. Animals subjected to the longer ischemic episodes had massive necrosis of pyramidal CA1 cells of the hippocampus, while animals receiving double ischemia (2 + 10 min) showed neuronal tolerance to the ischemic insult. ATP-diphosphohydrolase activity from hippocampal synaptosomes was assayed in these three groups (N = 6 animals/group) under two conditions: no reperfusion and 5-min of reperfusion. The control values for ATPase and ADPase activities were 144.7 +/- 18.8 and 60.6 +/- 5.24 nmol Pi min-1 mg protein-1, respectively. The 10-min group without reperfusion showed an enhancement of approximately 20 for ATPase and ADPase activities. In reperfused rats, only the 2-min group had a 20 increase in both enzymatic activities. We suggest that modulation of ATP-diphosphohydrolase activity might be involved in molecular events that follow both ischemia and reperfusion.