Repetitive Diffuse Mild Traumatic Brain Injury Causes an Atypical Astrocyte Response and Spontaneous Recurrent Seizures

• DOI: 10.1523/jneurosci.1067-18.2018
• Publication Date: 2019-01-21T23:05:14Z
• Authors: Oleksii Shandra; Alexander R. Wine...; Benjamin P. Heithoff; Carmen Munoz-Ball...; Kijana K. George; Michael J. Benko; Ivan A. Zuidhoek; Michelle N. Besser; Dallece E. Curley; G. Franklin Edwards; Anroux Mey; Alexys N. Harrington; Jeremy P. Kitchen; Stefanie Robel
• Keywords: Astrogliosis; Glial scar; Gliosis; Brain damage

Focal traumatic brain injury (TBI) induces astrogliosis, a process essential to protecting uninjured areas from secondary damage. However, astrogliosis can cause loss of astrocyte homeostatic functions and possibly contributes comorbidities such as posttraumatic epilepsy (PTE). Scar-forming astrocytes seal focal injuries off healthy tissue. It is these glial scars that are associated with originating in the cerebral cortex hippocampus. vast majority human TBIs also present diffuse caused by acceleration-deceleration forces leading tissue shearing. The resulting damage may be intrinsically different lesions would trigger scar formation. Here, we used mice both sexes model repetitive mild/concussive closed-head TBI, which only induced injury, test hypothesis respond uniquely TBI sufficient PTE. Astrocytes did not form classic characterized upregulation fibrillary acidic protein was limited. Surprisingly, an unrelated population atypical reactive lack expression, rapid sustained downregulation proteins impaired coupling. After latency period, subset developed spontaneous recurrent seizures reminiscent PTE patients. Seizing had larger compared nonseizing mice, suggesting might contribute epileptogenesis after TBI. SIGNIFICANCE STATEMENT Traumatic acquired epilepsies. Reactive have long been patients, particularly focal/lesional injury. most include nonfocal, injuries. showed for development mice. We identified response coupling while markers or formation absent. Areas were animals later this one root