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1.
Open Biol ; 13(12): 230253, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38052249

RESUMEN

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.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Demencia , Humanos , Anciano , Componente Amiloide P Sérico/química , Componente Amiloide P Sérico/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Encéfalo/metabolismo , Proteínas Sanguíneas/metabolismo , Demencia/metabolismo , Péptidos beta-Amiloides/metabolismo
4.
J Neurotrauma ; 34(9): 1766-1777, 2017 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-27881040

RESUMEN

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.


Asunto(s)
Ácidos Docosahexaenoicos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/rehabilitación , Animales , Vértebras Cervicales/lesiones , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Grasos Omega-3/uso terapéutico , Femenino , Inmunohistoquímica , Locomoción , Destreza Motora , Regeneración Nerviosa/efectos de los fármacos , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Plasticidad Neuronal/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Tractos Piramidales/citología , Tractos Piramidales/efectos de los fármacos , Tractos Piramidales/crecimiento & desarrollo , Ratas , Ratas Sprague-Dawley , Neuronas Serotoninérgicas/efectos de los fármacos , Sinaptofisina/biosíntesis , Sinaptofisina/genética
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