Cargando…

Serum amyloid P component accumulates and persists in neurones following traumatic brain injury

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 Aβ amyloid...

Descripción completa

Detalles Bibliográficos
Autores principales: Yip, Ping K., Liu, Zhou-Hao, Hasan, Shumaila, Pepys, Mark B., Uff, Christopher E. G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697800/
http://dx.doi.org/10.1098/rsob.230253
_version_ 1785154812650717184
author Yip, Ping K.
Liu, Zhou-Hao
Hasan, Shumaila
Pepys, Mark B.
Uff, Christopher E. G.
author_facet Yip, Ping K.
Liu, Zhou-Hao
Hasan, Shumaila
Pepys, Mark B.
Uff, Christopher E. G.
author_sort Yip, Ping K.
collection PubMed
description 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 Aβ amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of Aβ 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.
format Online
Article
Text
id pubmed-10697800
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher The Royal Society
record_format MEDLINE/PubMed
spelling pubmed-106978002023-12-06 Serum amyloid P component accumulates and persists in neurones following traumatic brain injury Yip, Ping K. Liu, Zhou-Hao Hasan, Shumaila Pepys, Mark B. Uff, Christopher E. G. Open Biol Research 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 Aβ amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of Aβ 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. The Royal Society 2023-12-06 /pmc/articles/PMC10697800/ http://dx.doi.org/10.1098/rsob.230253 Text en © 2023 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Yip, Ping K.
Liu, Zhou-Hao
Hasan, Shumaila
Pepys, Mark B.
Uff, Christopher E. G.
Serum amyloid P component accumulates and persists in neurones following traumatic brain injury
title Serum amyloid P component accumulates and persists in neurones following traumatic brain injury
title_full Serum amyloid P component accumulates and persists in neurones following traumatic brain injury
title_fullStr Serum amyloid P component accumulates and persists in neurones following traumatic brain injury
title_full_unstemmed Serum amyloid P component accumulates and persists in neurones following traumatic brain injury
title_short Serum amyloid P component accumulates and persists in neurones following traumatic brain injury
title_sort serum amyloid p component accumulates and persists in neurones following traumatic brain injury
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697800/
http://dx.doi.org/10.1098/rsob.230253
work_keys_str_mv AT yippingk serumamyloidpcomponentaccumulatesandpersistsinneuronesfollowingtraumaticbraininjury
AT liuzhouhao serumamyloidpcomponentaccumulatesandpersistsinneuronesfollowingtraumaticbraininjury
AT hasanshumaila serumamyloidpcomponentaccumulatesandpersistsinneuronesfollowingtraumaticbraininjury
AT pepysmarkb serumamyloidpcomponentaccumulatesandpersistsinneuronesfollowingtraumaticbraininjury
AT uffchristophereg serumamyloidpcomponentaccumulatesandpersistsinneuronesfollowingtraumaticbraininjury