microdissection-mouse-brain-into-functionally-anatomically-different

Microdissection of Mouse Brain into Functionally and Anatomically Different Regions

The brain is the command center for the mammalian nervous system and an organ with enormous structural complexity. Protected within the skull, the brain ...

Walter Reed Army Institute of Research, Medical Readiness Systems Biology, Center for Military Psychiatry and Neuroscience

The degree of brain injury is the governing factor for the magnitude of the patient's psycho- and physiological deficits post-injury, and the associated long-term consequences. The present scaling method used to segregate the patients among mild, moderate and severe phases of traumatic brain injury (TBI) has major limitations; however, a more continuous stratification of TBI is still elusive. With the anticipation that differentiating molecular markers could be the backbone of a robust method to triage TBI, we used a modified closed-head injury (CHI) Marmarou model with two impact heights (IH). By definition, IH directly correlates with the impact force causing TBI. In our modified CHI model, the rat skull was fitted with a helmet to permit a diffuse axonal injury. With the frontal cortex as the focal point of injury, the adjacent brain regions (hippocampus, HC and cerebellum, CB) were susceptible to diffuse secondary shock injury. At 8 days post injury (po.i.), rats impacted by 120 cm IH (IH) took a longer time to find an escape route in the Barnes maze as compared to those impacted by 100 cm IH (IH). Using a time-resolved interrogation of the transcriptomic landscape of HC and CB tissues, we mined those genes that altered their regulations in correlation with the variable IHs. At 14 days po.i., when all rats demonstrated nearly normal visuomotor performance, the bio-functional analysis suggested an advanced healing mechanism in the HC of IH group. In contrast, the HC of IH group displayed a delayed healing with evidence of active cell death networks. Combining whole genome rat microarrays with behavioral analysis provided the insight of neuroprotective signals that could be the foundation of the next generation triage for TBI patients.

Nabarun Chakraborty

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