Traumatic Brain Injury Tissue Research Articles

Novel treatment of intracerebral hemorrhage with mechanical tissue resuscitation.

The previous laboratory and clinical experience of the authors had demonstrated that application of controlled subatmospheric pressure directly to injured soft tissue can result in increased survival of compromised tissues. Mechanical tissue resuscitation (MTR) is a new concept evolving from these discoveries. The authors' recent studies have demonstrated that traumatic brain injury tissue can also be salvaged. The aim of this study was to examine the effects of MTR application to injuries from intracerebral hemorrhages (ICHs) in a swine model. The ICHs in swine were simulated by infusion of autologous artery blood into the right frontal lobe. A specially designed silicone manifold device was introduced directly into the hematoma. Continuous negative pressure at -50 mm Hg was applied through this device. T2- and T2*-weighted MRI, histological H&E staining, and immunostaining were examined. After 1 week of treatment, MTR significantly decreased gross hematoma volume by more than 60%, from 472.62 ± 230.19 mm3 in the nontreated group to 171.25 ± 75.38 mm3 in the MTR-treated group (p < 0.05). Total hypointense volumes measured on T2*-weighted MR images decreased from 791.99 ± 360.47 mm3 in the nontreated group to 371.16 ± 105.75 mm3 in the MTR-treated group (p < 0.05). The hyperintense area on the T2-weighted MR image decreased significantly from 2656.23 ± 426.26 mm3 in the nontreated group to 1816.66 ± 525.26 mm3 in the MTR-treated group (p < 0.05). When ICHs were treated with MTR for 2 weeks, the gross hematomas were reduced by 94%, from 112.23 ± 66.21 mm3 in the nontreated group to 6.12 ± 10.99 mm3 in the MTR-treated group (p = 0.003). MTR significantly decreased the total necrotic tissue volume in H&E staining from 120.42 ± 48.35 mm3 in the nontreated group to 60.94 ± 38.99 mm3 in the MTR-treated group (p < 0.05). The total hypointense volumes on T2*-weighted MR images were significantly reduced, from 385.54 ± 93.85 mm3 in the nontreated group to 220.54 ± 104.28 mm3 in the MTR-treated group (p < 0.05), while their mean T2 hyperintense volume decreased significantly from 2192.83 ± 728.27 mm3 in the nontreated group to 1366.97 ± 463.36 mm3 in the MTR-treated group (p < 0.05). Histology revealed that the capillary diameter in the reactive tissue rim adjacent to the hematoma increased in both the 1- and 2-week MTR-treated groups. Both von Willebrand factor and CD31 signals were detectable in endothelial cells within the hematoma cavity of both MTR-treated groups. This study demonstrates that local continuous application of controlled subatmospheric pressure to an ICH can safely remove more than half of a clot in 1 week and more than 90% in 2 weeks.

Effect of brain traumatic tissue extract on the survival and differentiation of neural stem cells

Objective To simulate the chemical microenvironment after traumatic brain injury (TBI) and to investigate the effect of this microenvironment on the survival and differentiation of neural stem cells (NSCs). Methods The brain tissue homogenate of TBI rat model was harvested to simulate the chemical microenvironment after TBI. The primary NSCs of rat model were isolated and extraction, and then identified the phenotype characteristics with immunofluorescence staining. The experiments were divided into control group, normal brain tissue extract group (BTE group) and traumatic brain injury tissue extract group (TBITE group). The cell growth and morphological changes of each group were observed dynamically. The expression of apoptosis related protein, which includes Bax, Bcl-2, caspase-3 and cleaved caspase-3, were detected by Western Blot 24 h after experiments. The proliferation of NSCs was detected by MTT assay and Western Blot after 3 days. The differentiation level of NSCs to neurons was detected by immunofluorescence staining after 7 days. Results The results of Western Blot showed that compared with the control group, there was no significant change of apoptosis in the BTE group, while the apoptosis in the BTE group was significantly increased, showed a increase of expression levels of Bax (F=18.06, P<0.01) and Cleaved caspase-3 (F=23.86, P<0.01), and a decrease of that of Bcl-2 (F=22.95, P<0.01). The results of MTT assay showed that compared with the BTE group, the proliferation of NSCs in the TBITE group was decreased (F=41.99, P<0.01). The immunofluorescence staining showed that compared with the control group, the neuronal differentiation rate was increased in the BTE group. Further, compared with the BTE group, the neuronal differentiation rate in the TBITE group was decreased (F=66.93, P<0.01). Conclusion The injury microenvironment after TBI can significantly inhibit the survival and differentiation of NSCs, which provides a theoretical basis for clarifying the mechanism of endogenous nerve regeneration after TBI. Key words: Traumatic brain injury; Chemical microenvironment; Neural stem cells; Brain tissue extract