Brain Injury Forces of Moderate Magnitude Elicit the Fencing Response

Self Cite

100

In diffuse brain-injured rats, robust sensory sensitivity to manual whisker stimulation develops over 1 month post-injury, comparable to agitation expressed by brain-injured individuals with overstimulation. In the rat, whisker somatosensation relies on thalamocortical glutamatergic relays between the ventral posterior medial (VPM) thalamus and barrel fields of somatosensory cortex (S1BF). Using novel glutamate-selective microelectrode arrays coupled to amperometry, we test the hypothesis that disrupted glutamatergic neurotransmission underlies the whisker sensory sensitivity associated with diffuse brain injury. We report hypersensitive glutamate neurotransmission that parallels and correlates with the development of post-traumatic sensory sensitivity. Hypersensitivity is demonstrated by significant 110% increases in VPM extracellular glutamate levels, and 100% increase in potassium-evoked glutamate release in the VPM and S1BF, with no change in glutamate clearance. Further, evoked glutamate release showed 50% greater sensitivity to a calcium channel antagonist in braininjured over uninjured VPM. In conjunction with no changes in glutamate transporter gene expression and exogenous glutamate clearance efficiency, these data support a presynaptic origin for enduring post-traumatic circuit alterations. In the anatomically-distinct whisker circuit, the injury-induced functional alterations correlate with the development of late-onset behavioral morbidity. Effective therapies to modulate presynaptic glutamate function in diffuse-injured circuits may translate into improvements in essential brain function and behavioral performance in other brain-injured circuits in rodents and in humans.

Section: Diffuse Brain Injury: Midline Fluid Percussion Injury (Mfpi)mentioning

confidence: 99%

Hypersensitive Glutamate Signaling Correlates with the Development of Late-Onset Behavioral Morbidity in Diffuse Brain-Injured Circuitry

Thomas

Hinzman

Gerhardt

et al. 2012

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100

“…Adult male Sprague-Dawley rats (350-375 g) were subjected to midline fluid percussion injury (FPI) consistent with methods described previously (Hosseini and Lifshitz, 2009;Lifshitz et al, 2007a;Lifshitz, 2008). Final animal numbers are indicated in the results section for each study.…”

Section: Midline Fluid Percussion Brain Injurymentioning

confidence: 99%

“…As reflexive responses returned, an injury of moderate (1.9-2.0 atm) or mild severity (1.1-1.2 atm) was administered by releasing the pendulum onto the fluid-filled cylinder. The animals were monitored for the presence of a forearm fencing response and the return of the righting reflex as indicators of injury severity (Hosseini and Lifshitz, 2009). Sham animals were connected to the FPI device, but the pendulum was not released.…”

Section: Midline Fluid Percussion Brain Injurymentioning

confidence: 99%

The Whisker Nuisance Task Identifies a Late-Onset, Persistent Sensory Sensitivity in Diffuse Brain-Injured Rats

McNamara

Lisembee

Lifshitz

2010

Self Cite

167

Post-traumatic morbidity reduces the quality of life for traumatic brain injury (TBI) survivors by altering neuropsychological function. After midline fluid percussion injury (FPI), diffuse pathology in the ventral posterior thalamus suggests that somatosensory whisker function may be impaired post-injury. The goals of the present study were to design and validate a task to detect injury-induced somatosensory morbidity (Experiment 1), and to evaluate preliminary applications of the task (Experiment 2). In Experiment 1, male Sprague-Dawley rats were subjected to moderate FPI (*1.9 atm) or sham injury. Over an 8-week time course, the whiskers on both mystacial pads were stimulated manually with an applicator stick in an open field for three 5-min periods. Behavioral responses in this whisker nuisance task were recorded using objective criteria (max score ¼ 16). Sham animals were ambivalent or soothed by whisker stimulation (4.0 AE 0.8), whereas brain-injured rats showed aggravated responses at 1 week (6.7 AE 0.9), which became significant at 4 weeks (9.5 AE 0.5) and 8 weeks (8.4 AE 1.1) compared to sham injury, indicating chronic injury-induced sensory sensitivity. Total free serum corticosterone levels indicated a significant stress response in brain-injured (125.0 AE 17.7 ng=mL), but not uninjured animals (74.2 AE 12.2 ng=mL) in response to whisker stimulation. In Experiment 2, to evaluate applications of the whisker nuisance task, four additional uninjured and brain-injured groups were subjected to mild brain injury only, shaved whiskers after moderate brain injury, repeated whisker nuisance task stimulation after moderate brain injury, or regular opportunities for tactile exploration of an enriched environment after moderate brain injury over 4 weeks post-injury. The whisker nuisance task has the sensitivity to detect mild brain injury (7.7 AE 1.0), but morbidity was not mitigated by any of the neurorehabilitative interventions. Following diffuse brain injury, the whisker nuisance task is a promising tool to detect post-traumatic morbidity and the efficacy of therapeutic interventions that may restore discrete circuit function in brain-injured patients.

“…60 This extension of one limb concurrent with flexion of the contralateral limb is associated with longer suppression of the righting reflex in FPI in rats and occurs in two-thirds of sports concussions resulting in LOC. Translational features such as the fencing response may facilitate evaluation of interventions for acute mTBI.…”

Section: Mtbi Experimental Modelsmentioning

confidence: 93%

Mild Traumatic Brain Injury in Translation

Levin

Robertson

2013

This Introduction to a Special Issue on Mild Traumatic Brain Injury (mTBI) highlights the methodological challenges in outcome studies and clinical trials involving patients who sustain mTBI. Recent advances in brain imaging and portable, computerized cognitive tasks have contributed to protocols that are sensitive to the effects of mTBI and efficient in time for completion. Investigation of civilian mTBI has been extended to single and repeated injuries in athletes and blastrelated mTBI in service members and veterans. Despite differences in mechanism of injury, there is evidence for similar effects of acceleration-deceleration and blast mechanisms of mTBI on cognition. Investigation of repetitive mTBI suggests that the effects may be cumulative and that repeated mTBI and repeated subconcussive head trauma may lead to neurodegenerative conditions. Although animal models of mTBI using cortical impact and fluid percussion injury in rodents have been able to reproduce some of the cognitive deficits frequently exhibited by patients after mTBI, modeling post-concussion symptoms is difficult. Recent use of closed head and blast injury animal models may more closely approximate clinical mTBI. Translation of interventions that are developed in animal models to patients with mTBI is a priority for the research agenda. This Special Issue on mTBI integrates basic neuroscience studies using animal models with studies of human mTBI, including the cognitive sequelae, persisting symptoms, brain imaging, and host factors that facilitate recovery.