Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats.

Traumatic brain injury-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines, especially epinephrine, although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury. Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate, blood pressure, and blood flow to the hindlimb muscles. Therefore, the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in several function-specific central nervous system regions in rats.

Effect of Simultaneous Combined Treadmill Training and Magnetic Stimulation on Spasticity and Gait Impairments after Cervical Spinal Cord Injury.

Cervical spinal cord injury (CSCI) can induce lifelong disabilities, including spasticity and gait impairments. The objective of this pre-clinical study was to evaluate the therapeutic effects of simultaneous and combined early locomotor treadmill training (Tm) and injury site magnetic stimulation (TMSsc) on spasticity and gait impairments in a rat model of C moderate contusion SCI. The Tm training was initiated at post-injury (PI) day 8, whereas TMS treatment was added to Tm 14 days PI, and then the combined therapy (TMSTm) was continued for six weeks.

Mild closed head traumatic brain injury-induced changes in monoamine neurotransmitters in the trigeminal subnuclei of a rat model: mechanisms underlying orofacial allodynias and headache.

Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias, a hypersensitive pain response induced by non-painful stimulation. These allodynias, tested using thermal hyperalgesia, correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway, especially in the trigeminal nucleus caudalis. This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis, pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury, which are related to tactile allodynia, touch-pressure sensitivity, and visceral pain.

Mild and Mild-to-Moderate Traumatic Brain Injury-Induced Significant Progressive and Enduring Multiple Comorbidities.

Traumatic brain injury (TBI) can produce life-long disabilities, including anxiety, cognitive, balance, and motor deficits. The experimental model of closed head TBI (cTBI) induced by weight drop/impact acceleration is known to produce hallmark TBI injuries. However, comprehensive long-term characterization of comorbidities induced by graded mild-to- mild/moderate intensities using this experimental cTBI model has not been reported.

Closed-Head TBI Model of Multiple Morbidity.

Successful therapy for TBI disabilities awaits refinement in the understanding of TBI neurobiology, quantitative measurement of treatment-induced incremental changes in recovery trajectories, and effective translation to human TBI using quantitative methods and protocols that were effective to monitor recovery in preclinical models. Details of the specific neurobiology that underlies these injuries and effective quantitation of treatment-induced changes are beginning to emerge utilizing a variety of preclinical and clinical models (for reviews see (Morales et al., Neuroscience 136:971-989, 2005; Fujimoto et al.

Prolonged hippocampal cell death following closed-head traumatic brain injury in rats.

Traumatic brain injury (TBI) leads to enduring cognitive disorders. Although recent evidence has shown that controlled cortical impact in a rodent may induce memory deficits with prolonged cell death in the dentate gyrus (DG) of the hippocampus, few studies have reported long-term chronic hippocampal cell death following 'closed-head' TBI (cTBI), the predominant form of human TBI. Therefore, the aim of this study was to quantify terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)(+) apoptotic hippocampal cells as well as hippocampal cells with hallmark morphological features of degenerating cells in a chronic setting of cTBI in rats.

Trigeminal neuroplasticity underlies allodynia in a preclinical model of mild closed head traumatic brain injury (cTBI).

Post-traumatic headache (PTH) following TBI is a common and often persisting pain disability. PTH is often associated with a multimodal central pain sensitization on the skin surface described as allodynia. However, the particular neurobiology underlying cTBI-induced pain disorders are not known.

Effect of combined treadmill training and magnetic stimulation on spasticity and gait impairments after cervical spinal cord injury.

Spasticity and gait impairments are two common disabilities after cervical spinal cord injury (C-SCI). In this study, we tested the therapeutic effects of early treadmill locomotor training (Tm) initiated at postoperative (PO) day 8 and continued for 6 weeks with injury site transcranial magnetic stimulation (TMSsc) on spasticity and gait impairments after low C6/7 moderate contusion C-SCI in a rat model. The combined treatment group (Tm+TMSsc) showed the most robust decreases in velocity-dependent ankle torques and triceps surae electromyography burst amplitudes that were time locked to the initial phase of lengthening, as well as the most improvement in limb coordination quantitated using three-dimensional kinematics and CatWalk gait analyses, compared to the control or single-treatment groups.

Effects of acute intrathecal baclofen in an animal model of TBI-induced spasticity, cognitive, and balance disabilities.

Spasticity is a major health problem for patients with traumatic brain injury (TBI). In addition to spasticity, TBI patients exhibit enduring cognitive, balance, and other motor impairments. Although the use of antispastic medications, particularly ITB, can decrease the severity of TBI-induced spasticity, current guidelines preclude the use of ITB during the first year after TBI.

Altered patterns of reflex excitability, balance, and locomotion following spinal cord injury and locomotor training.

Spasticity is an important problem that complicates daily living in many individuals with spinal cord injury (SCI). While previous studies in human and animals revealed significant improvements in locomotor ability with treadmill locomotor training, it is not known to what extent locomotor training influences spasticity. In addition, it would be of considerable practical interest to know how the more ergonomically feasible cycle training compares with treadmill training as therapy to manage SCI-induced spasticity and to improve locomotor function.

Delayed synaptic transmission in Drosophila cacophonynull embryos.

Ca(2+) influx through the Drosophila N-type Ca(2+) channel, encoded by cacophony (cac), triggers fast synaptic transmission. We now ask whether the cac Ca(2+) channel is the Ca(2+) channel solely dedicated for fast synaptic transmission. Because the cac(null) mutation is lethal, we used cac(null) embryos to address this question.

Nerve-evoked synchronous release and high K+ -induced quantal events are regulated separately by synaptotagmin I at Drosophila neuromuscular junctions.

The distal Ca(2+)-binding domain of synaptotagmin I (Syt I), C2B, has two Ca(2+)-binding sites. To study their function in Drosophila, pairs of aspartates were mutated to asparagines and the mutated syt I was expressed in the syt I-null background (P[syt I(B-D1,2N)] and P[syt I(B-D3,4N)]). We examined the effects of these mutations on nerve-evoked synchronous synaptic transmission and high K(+)-induced quantal events at embryonic neuromuscular junctions.

Repetitive exposures to nicotine induce a hyper-responsiveness via the cAMP/PKA/CREB signal pathway in Drosophila.

Nicotine, in addition to acute effects, has long-lasting effects on mammalian behaviors, such as those leading to addiction. Here we present genetic and pharmacological evidence in Drosophila suggesting that repetitive exposures to nicotine induce a hyper-responsiveness through synthesis of new protein(s) via CREB-mediated gene transcription. Single exposure to volatilized nicotine dose-dependently inhibited the startle-induced climbing response.