학술논문
Microglia inflict delayed brain injury after subarachnoid hemorrhage
Original Paper
Original Paper
Document Type
Academic Journal
Author
Source
Acta Neuropathologica. August 2015, Vol. 130 Issue 2, p215, 17 p.
Subject
Language
English
ISSN
0001-6322
Abstract
Author(s): Ulf C. Schneider[sup.1] [sup.2] , Anja-Maria Davids[sup.1] [sup.2] , Susan Brandenburg[sup.2] , Annett Müller[sup.2] , Anna Elke[sup.2] , Salima Magrini[sup.2] , Etienne Atangana[sup.2] [sup.3] , Kati Turkowski[sup.2] , Tobias [...]
Inflammatory changes have been postulated to contribute to secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH). In human specimens after SAH as well as in experimental SAH using mice, we show an intracerebral accumulation of inflammatory cells between days 4 and 28 after the bleeding. Using bone marrow chimeric mice allowing tracing of all peripherally derived immune cells, we confirm a truly CNS-intrinsic, microglial origin of these immune cells, exhibiting an inflammatory state, and rule out invasion of myeloid cells from the periphery into the brain. Furthermore, we detect secondary neuro-axonal injury throughout the time course of SAH. Since neuronal cell death and microglia accumulation follow a similar time course, we addressed whether the occurrence of activated microglia and neuro-axonal injury upon SAH are causally linked by depleting microglia in vivo. Given that the amount of neuronal cell death was significantly reduced after microglia depletion, we conclude that microglia accumulation inflicts secondary brain injury after SAH.
Inflammatory changes have been postulated to contribute to secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH). In human specimens after SAH as well as in experimental SAH using mice, we show an intracerebral accumulation of inflammatory cells between days 4 and 28 after the bleeding. Using bone marrow chimeric mice allowing tracing of all peripherally derived immune cells, we confirm a truly CNS-intrinsic, microglial origin of these immune cells, exhibiting an inflammatory state, and rule out invasion of myeloid cells from the periphery into the brain. Furthermore, we detect secondary neuro-axonal injury throughout the time course of SAH. Since neuronal cell death and microglia accumulation follow a similar time course, we addressed whether the occurrence of activated microglia and neuro-axonal injury upon SAH are causally linked by depleting microglia in vivo. Given that the amount of neuronal cell death was significantly reduced after microglia depletion, we conclude that microglia accumulation inflicts secondary brain injury after SAH.