Selective Brain Hypothermia Mitigates Brain Damage and Improves Neurological Outcome after Post-Traumatic Decompressive Craniectomy in Mice

Abstract

Hypothermia and decompressive craniectomy (DC) have been considered as treatment for traumatic brain injury. The present study investigates whether selective brain hypothermia added to craniectomy could improve neurological outcome after brain trauma. Male CD-1 mice were assigned into the following groups: sham; DC; closed head injury (CHI); CHI followed by craniectomy (CHI+DC); and CHI+DC followed by focal hypothermia (CHI+DC+H). At 24 h post-trauma, animals were subjected to Neurological Severity Score (NSS) test and Beam Balance Score test. At the same time point, magnetic resonance imaging using a 9.4 Tesla scanner and subsequent volumetric evaluation of edema and contusion were performed. Thereafter, the animals were sacrificed and subjected to histopathological analysis. According to NSS, there was a significant impairment among all the groups subjected to trauma. Animals with both trauma and craniectomy performed significantly worse than animals with craniectomy alone. This deleterious effect disappeared when additional hypothermia was applied. BBS was significantly worse in the CHI and CHI+DC groups, but not in the CHI+DC+H group, compared to the sham animals. Edema and contusion volumes were significantly increased in CHI+DC animals, but not in the CHI+DC+H group, compared to the DC group. Histopathological analysis showed that neuronal loss and contusional blossoming could be attenuated by application of selective brain hypothermia. Selective brain cooling applied post-trauma and craniectomy improved neurological function and reduced structural damage and may be therefore an alternative to complication-burdened systemic hypothermia. Clinical studies are recommended in order to explore the potential of this treatment.

iTRAQ-Based Quantitative Proteomics Reveals the New Evidence Base for Traumatic Brain Injury Treated with Targeted Temperature Management

“…Similar to our previous studies and other reports, TBI produces behavioral abnormalities and neurodegenerative changes resulting from regional patterns of cell death and circuit dysfunction [21,44]. As supported by previous studies of TTM on TBI, we also demonstrated that using CCI rats as an in vivo model that TTM attenuated several phenotypes of animal post-TBI, markedly reduced cell death [7,8,11], BBB leakage [45][46][47], cortical lesion volume [48], cerebrovascular histopathology [49,50], and improved behavioral and pathological outcomes [51]. These results may help determine both the safety and efficacy for postinjury TTM, and such laboratory models (in vitro or in vivo) may present an ideal opportunity for the application of proteomic technological approach to biomarker discovery after TBI.…”

Changes in Posttraumatic Brain Edema in Craniectomy-Selective Brain Hypothermia Model Are Associated With Modulation of Aquaporin-4 Level

“…To achieve reported neuroprotective effects of hypothermia without risk of previously mentioned systemic side effects, selective, or focal brain cooling got into focus. Some previous studies (conducted also by our group, see Figure 1 ) were able to report a limitation of brain edema formation due to focal application of hypothermia ( 20 , 39 – 45 ).…”

Direct Brain Cooling in Treating Severe Traumatic Head Injury

“…There are previously multiple papers that suggested targeted brain cooling as a reasonable treatment option to patient with severe traumatic brain injury [21][22][23][24][25][26][27][28][29][30][31][32][33]. Targeted brain cooling is a good alternative to systemic hypothermia, as systemic hypothermia has serious side effects such as circulatory constrain, increased risk of infection, electrolyte imbalance, and coagulopathy [15][16][17][18].…”

“…Jacek et al [33] suggested in their animal study that selective brain hypothermia, which is applied via a cranial window after decompressive craniectomy seems to be reducing posttraumatic structural and functional damage. However, the study is actually limited by small rodent model and also short observational period.…”