Pharyngeal Selective Brain Cooling Improves Neurofunctional and Neurocognitive Outcome after Fluid Percussion Brain Injury in Rats

Doll, Hinnerk; Truebel, Hubert; Kipfmueller, Florian; Schaefer, Ute; Neugebauer, Edmund; Wirth, Stéfan; Maegele, Marc

doi:10.1089/neu.2008.0741

Cited by 22 publications

(13 citation statements)

References 49 publications

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“…Finally, the shorter latency to fall by LFP mice relative to sham mice in the rotarod paradigm up to 3 weeks following mild injury is an indicator of deficits in integrated vestibulomotor and sensorimotor function. A more moderate injury would reveal more striking changes in cognitive and motor function as has been shown by other groups [27][28][29][30] .…”

Section: Discussionmentioning

confidence: 58%

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

Alder

Fujioka

Lifshitz

et al. 2011

JoVE

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Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes 1,2 . Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement 3,4 . The resulting hematomas and lacerations cause a vascular response 3,5 , and the morphological and functional damage of the white matter leads to diffuse axonal injury [6][7][8] . Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure . Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals [10][11][12] , which ultimately result in long-term neurological disabilities 13,14 . Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair.Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration 1 . The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue 1,15 . Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure 16,17 . The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed skull 18 . Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury 19. It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation 20 .We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP. Video LinkThe video component of this article can be found at https://www.jove.com/video/3063/ Protocol 1. Craniectomy 1. A sterile surgical site is prepared including a stereotaxic alignment instrument (Kopf Instruments) for mice with a mouse gas anesthesia head holder (Kopf Instruments) connected to an anesthesia machine with O 2 flush (Parkland Scientific) to allow for continuou...

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Section: Discussionmentioning

confidence: 58%

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

Alder

Fujioka

Lifshitz

et al. 2011

JoVE

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“…Barnes maze was used to assess spatial learning and memory (Barnes, 1979; Maegele et al, 2005; Doll et al, 2009). BM represents a widely used, validated, and less stressful alternative to the commonly used water maze test (Harrison et al, 2009).…”

Section: Methodsmentioning

confidence: 99%

Stress and Traumatic Brain Injury: A Behavioral, Proteomics, and Histological Study

Kwon¹,

Kövesdi²,

György³

et al. 2011

Front. Neur.

112

119

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Psychological stress and traumatic brain injury (TBI) can both result in lasting neurobehavioral abnormalities. Post-traumatic stress disorder and blast induced TBI (bTBI) have become the most significant health issues in current military conflicts. Importantly, military bTBI virtually never occurs without stress. In this experiment, we assessed anxiety and spatial memory of rats at different time points after repeated exposure to stress alone or in combination with a single mild blast. At 2 months after injury or sham we analyzed the serum, prefrontal cortex (PFC), and hippocampus (HC) of all animals by proteomics and immunohistochemistry. Stressed sham animals showed an early increase in anxiety but no memory impairment at any measured time point. They had elevated levels of serum corticosterone (CORT) and hippocampal IL-6 but no other cellular or protein changes. Stressed injured animals had increased anxiety that returned to normal at 2 months and significant spatial memory impairment that lasted up to 2 months. They had elevated serum levels of CORT, CK-BB, NF-H, NSE, GFAP, and VEGF. Moreover, all of the measured protein markers were elevated in the HC and the PFC; rats had an increased number of TUNEL-positive cells in the HC and elevated GFAP and Iba1 immunoreactivity in the HC and the PFC. Our findings suggest that exposure to repeated stress alone causes a transient increase in anxiety and no significant memory impairment or cellular and molecular changes. In contrast, repeated stress and blast results in lasting behavioral, molecular, and cellular abnormalities characterized by memory impairment, neuronal and glial cell loss, inflammation, and gliosis. These findings may have implications in the development of diagnostic and therapeutic measures for conditions caused by stress or a combination of stress and bTBI.

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“…reclinical research has consistently demonstrated that therapeutic hypothermia is a promising neuroprotective strategy for treating traumatic brain injury (TBI) by effectively reducing injury-induced increases in intracranial pressure, cellular damage, and improving neurological outcomes (Fingas et al, 2007;Doll et al, 2009;Dietrich and Bramlett, 2010;Wei et al, 2011). In contrast, clinical studies have yielded less consistent results and failed to establish a standardized hypothermia strategy for treating severe TBI patients (McIntyre et al, 2003;Hutchison et al, 2008;Grande et al, 2009;Adelson et al, 2013).…”

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confidence: 99%

Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury

Shear

Deng-Bryant

et al. 2016

Therapeutic Hypothermia and Temperature Management

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Brain hypothermia has been considered as a promising alternative to whole-body hypothermia in treating acute neurological disease, for example, traumatic brain injury. Previously, we demonstrated that 2-hours selective brain cooling (SBC) effectively mitigated acute (p24 hours postinjury) neurophysiological dysfunction induced by a penetrating ballistic-like brain injury (PBBI) in rats. This study evaluated neuroprotective effects of extended SBC (4 or 8 hours in duration) on sub-acute secondary injuries between 3 and 21 days postinjury (DPI). SBC (34°C) was achieved via extraluminal cooling of rats' bilateral common carotid arteries (CCA). Depending on the experimental design, SBC was introduced either immediately or with a 2-or 4-hour delay after PBBI and maintained for 4 or 8 hours. Neuroprotective effects of SBC were evaluated by measuring brain lesion volume, axonal injury, neuroinflammation, motor and cognitive functions, and post-traumatic seizures. Compared to untreated PBBI animals, 4 or 8 hours SBC treatment initiated immediately following PBBI produced comparable neuroprotective benefits against PBBI-induced early histopathology at 3 DPI as evidenced by significant reductions in brain lesion volume, axonal pathology (beta-amyloid precursor protein staining), neuroinflammation (glial fibrillary acetic protein stained-activated astrocytes and rat major histocompatibility complex class I stained activated microglial cell), and post-traumatic nonconvulsive seizures. In the later phase of the injury (7-21 DPI), significant improvement on motor function (rotarod test) was observed under most SBC protocols, including the 2-hour delay in SBC initiation. However, SBC treatment failed to improve cognitive performance (Morris water maze test) measured 13-17 DPI. The protective effects of SBC on delayed axonal injury (silver staining) were evident out to 14 DPI. In conclusion, the CCA cooling method of SBC produced neuroprotection measured across multiple domains that were evident days/weeks beyond the cooling duration and in the absence of overt adverse effects. These ''proof-of-concept'' results suggest that SBC may provide an attractive neuroprotective approach for clinical considerations.

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Pharyngeal Selective Brain Cooling Improves Neurofunctional and Neurocognitive Outcome after Fluid Percussion Brain Injury in Rats

Cited by 22 publications

References 49 publications

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

Stress and Traumatic Brain Injury: A Behavioral, Proteomics, and Histological Study

Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury

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