The Effect of Hypothermia on the Expression of TIMP-3 after Traumatic Brain Injury in Rats

Feng, Jia; Mao, Qing; Liang, Yao; Jiang, Jiyao

doi:10.1089/neu.2008.0814

Cited by 13 publications

(5 citation statements)

References 45 publications

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“…In the fluid percussion TBI rat model, it was shown that the apoptosis-regulating protein TIMP-3 increased in normothermic group and reduced in hypothermic group (Jia, et al, 2012). This is consistent with our observation that HPI201 suppresses pro-apoptosis genes and increasing anti-apoptotic genes.…”

Section: Discussionmentioning

confidence: 99%

Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats

Wei

Espinera

et al. 2015

Experimental Neurology

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Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A six-hour hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15 min or 2 hr after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and Caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201 treated group exhibited improved functional recovery after TBI versus controls. These data support that PIH therapy using our NTR agonist is effective in reducing neuronal and BBB damage, attenuating inflammatory response and detrimental cellular signaling, and promoting functional recovery after TBI in the developing brain, supporting its potential for further evaluation towards clinical development.

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Section: Discussionmentioning

confidence: 99%

Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats

Wei

Espinera

et al. 2015

Experimental Neurology

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“…Interestingly, in humans TIMP-1 levels correlated with increased mortality and served as a possible biomarker for injury severity (Lorente et al, 2014). TIMP-3 is another member of this family that was found to be elevated in both injured and uninjured brain hemispheres after fluid percussion injury in rats - a response that was blocked by mild hypothermia (Jia et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

Jassam

Izzy

Whalen

et al. 2017

Neuron

586

496

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SUMMARY Traumatic brain injury (TBI) is a leading cause of morbidity and disability, with a considerable socioeconomic burden. Heterogeneity of pathoanatomical subtypes and diversity in the pathogenesis and extent of injury contribute to differences in the course and outcome of TBI. Following the primary injury, extensive and lasting damage is sustained through a complex cascade of events referred to as “secondary injury”. Neuroinflammation is proposed as an important manipulable aspect of secondary injury in animal and human studies. Because neuroinflammation can be detrimental or beneficial, before developing immunomodulatory therapies, it is necessary to better understand the timing and complexity of the immune responses that follows TBI. With a rapidly increasing body of literature, there is a need for a clear summary of TBI neuroimmunology. This review presents our current understanding of the immune response to TBI in a chronological and compartment-based manner, highlighting early changes in gene expression and initial signaling pathways that lead to activation of innate and adaptive immunity. Based on recent advances in our understanding of innate immune cell activation, we propose a new paradigm to study innate immune cells following TBI that moves away from the existing M1/M2 classification of activation states towards a stimulus and disease-specific understanding of polarization state based on transcriptomic and proteomic profiling.

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“…Preliminary achievements have been made regarding the treatment of TBI with hypothermia [20][21][22]; however, the effects of nontherapeutic, uncontrolled hypothermia on TBI are unclear. In the present study, we used a CCI mouse model to simulate TBI in a clinical setting, and LSCI was used to track and observe the changes in cerebral surface venous blood ow and microcirculation and to assess their relationship with cytokines.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Hemodynamic Changes Associated with Neuroinflammation under Seawater Immersion Hypothermia

Hou

Zhang

et al. 2023

Preprint

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Traumatic brain injury (TBI) combined with seawater immersion hypothermia (SIH) is one of the main causes of death and disability in shipwrecks. However, the impact of SIH on brain injury is still unclear. In this study, we used 8-week-old C57BL/6 mice to establish a controlled cortical impact model and simulate the hypothermia caused by seawater immersion after mice with TBI fell into seawater. The vital signs of the mouse model were continuously measured in the early stage of modeling, and the CBF of the mouse was recorded using laser scatter contrast imaging before and after modeling and after 6 and 24h. The cerebral cortex of 24h mice was collected for histopathological examination and enzyme-linked immunosorbent assay. The behavioral functions were assessed by behavioral analysis. The results showed that brain parenchymal injury was exacerbated during hypothermia in mice with TBI. CBF was significantly reduced in the hypothermic group compared with the normothermic group, and the levels of some inflammatory cytokines significantly increased and were correlated with low CBF. Overall, the results of this study suggested a correlation between inflammatory progression and low CBF, indicating that venous blood flow might be used for assessing neuroinflammatory progression after hypothermic trauma.

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The Effect of Hypothermia on the Expression of TIMP-3 after Traumatic Brain Injury in Rats

Cited by 13 publications

References 45 publications

Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats

Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

Cerebral Hemodynamic Changes Associated with Neuroinflammation under Seawater Immersion Hypothermia

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