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1.
Open Biol ; 13(12): 230253, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38052249

RESUMO

The mechanisms underlying neurodegenerative sequelae of traumatic brain injury (TBI) are poorly understood. The normal plasma protein, serum amyloid P component (SAP), which is normally rigorously excluded from the brain, is directly neurocytotoxic for cerebral neurones and also binds to Aß amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of Aß fibrils. Increased brain exposure to SAP is common to many risk factors for dementia, including TBI, and dementia at death in the elderly is significantly associated with neocortical SAP content. Here, in 18 of 30 severe TBI cases, we report immunohistochemical staining for SAP in contused brain tissue with blood-brain barrier disruption. The SAP was localized to neurofilaments in a subset of neurones and their processes, particularly damaged axons and cell bodies, and was present regardless of the time after injury. No SAP was detected on astrocytes, microglia, cerebral capillaries or serotoninergic neurones and was absent from undamaged brain. C-reactive protein, the control plasma protein most closely similar to SAP, was only detected within capillary lumina. The appearance of neurocytotoxic SAP in the brain after TBI, and its persistent, selective deposition in cerebral neurones, are consistent with a potential contribution to subsequent neurodegeneration.


Assuntos
Lesões Encefálicas Traumáticas , Demência , Humanos , Idoso , Componente Amiloide P Sérico/química , Componente Amiloide P Sérico/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Encéfalo/metabolismo , Proteínas Sanguíneas/metabolismo , Demência/metabolismo , Peptídeos beta-Amiloides/metabolismo
4.
J Neurotrauma ; 34(9): 1766-1777, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-27881040

RESUMO

Task-specific rehabilitation has been shown to promote functional recovery after acute spinal cord injury (SCI). Recently, the omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), has been shown to promote neuroplasticity after SCI. Here, we investigated whether the combination of a single bolus of DHA with rehabilitation can enhance the effect of DHA or rehabilitation therapy in adult injured spinal cord. We found enhanced functional improvement with DHA in combination with rehabilitation compared with either treatment alone in a rat cervical lateral hemisection SCI model. This behavioral improvement correlated with a significant sprouting of uninjured corticospinal and serotonergic fibers. We also observed that the greatest increase in the synaptic vesicle protein, synaptophysin, and the synaptic active zone protein, Bassoon, occurred in animals that received both DHA and rehabilitation. In summary, the functional, anatomical, and synaptic plasticity induced by task-specific rehabilitation can be further enhanced by DHA treatment. This study shows the potential beneficial effects of DHA combined with rehabilitation for the treatment of patients with SCI.


Assuntos
Ácidos Docosa-Hexaenoicos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/reabilitação , Animais , Vértebras Cervicais/lesões , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Imuno-Histoquímica , Locomoção , Destreza Motora , Regeneração Nervosa/efeitos dos fármacos , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Plasticidade Neuronal/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Tratos Piramidais/citologia , Tratos Piramidais/efeitos dos fármacos , Tratos Piramidais/crescimento & desenvolvimento , Ratos , Ratos Sprague-Dawley , Neurônios Serotoninérgicos/efeitos dos fármacos , Sinaptofisina/biossíntese , Sinaptofisina/genética
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