Targeting eIF2α in TBI-induced traumatic optic neuropathy: Effects of Salubrinal and the Integrated Stress Response Inhibitor.

Traumatic brain injury (TBI) can induce traumatic axonal injury in the optic nerve, which is referred to as traumatic optic neuropathy (TON). TON occurs in up to 5% of TBI cases and leads to irreversible visual deficits. TON-induced phosphorylation of eIF2α, a downstream ER stress activator in the PERK pathway presents a potential point for therapeutic intervention.

Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations: a scoping review.

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients. Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury, but relatively less is known about the effect in pediatric populations. The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibitors as a potential adjuvant treatment for neurocognitive decline in pediatric patients with traumatic brain injury.

Early Measures of TBI Severity Poorly Predict Later Individual Impairment in a Rat Fluid Percussion Model.

Background: Multiple measures of injury severity are suggested as common data elements in preclinical traumatic brain injury (TBI) research. The robustness of these measures in characterizing injury severity is unclear. In particular, it is not known how reliably they predict individual outcomes after experimental TBI.

Brief Oxygen Exposure after Traumatic Brain Injury Hastens Recovery and Promotes Adaptive Chronic Endoplasmic Reticulum Stress Responses.

Traumatic brain injury (TBI) is a major public health concern, particularly in adolescents who have a higher mortality and incidence of visual pathway injury compared to adult patients. Likewise, we have found disparities between adult and adolescent TBI outcomes in rodents. Most interestingly, adolescents suffer a prolonged apneic period immediately post-injury, leading to higher mortality; therefore, we implemented a brief oxygen exposure paradigm to circumvent this increased mortality.

Brief oxygen exposure after traumatic brain injury speeds recovery and promotes adaptive chronic endoplasmic reticulum stress responses.

Traumatic brain injury (TBI) is a major public health concern particularly in adolescents who have a higher mortality and incidence of visual pathway injury compared to adult patients. Likewise, we have found disparities between adult and adolescent TBI outcomes in rodents. Most interestingly, adolescents suffer a prolonged apneic period immediately post injury leading to higher mortality; so, we implemented a brief oxygen exposure paradigm to circumvent this increased mortality.

Attitudes and practices of specialty physicians regarding the return to school process after pediatric acquired brain injury.

Purpose: More than 50,000 children are hospitalized yearly in the U.S. for acquired brain injury (ABI) with no established standards or protocols for school re-entry and limited resources for hospital-school communication.

Chronic Histological Outcomes of Indirect Traumatic Optic Neuropathy in Adolescent Mice: Persistent Degeneration and Temporally Regulated Glial Responses.

Injury to the optic nerve, termed, traumatic optic neuropathy (TON) is a known comorbidity of traumatic brain injury (TBI) and is now known to cause chronic and progressive retinal thinning up to 35 years after injury. Although animal models of TBI have described the presence of optic nerve degeneration and research exploring acute mechanisms is underway, few studies in humans or animals have examined chronic TON pathophysiology outside the retina. We used a closed-head weight-drop model of TBI/TON in 6-week-old male C57BL/6 mice.

Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice.

Traumatic brain injury (TBI) results in a number of impairments, often including visual symptoms. In some cases, visual impairments after head trauma are mediated by traumatic injury to the optic nerve, termed traumatic optic neuropathy (TON), which has few effective options for treatment. Using a murine closed-head weight-drop model of head trauma, we previously reported in adult mice that there is relatively selective injury to the optic tract and thalamic/brainstem projections of the visual system.

Brachial plexus birth injuries and the association between pre-procedure and post-procedure pediatric outcomes data collection instrument scores and narakas classification.

Background: The brachial plexus is a network of nerves exiting the spinal cord through the fifth, sixth, seventh, and eighth cervical nerves (C5-C8) as well as the first thoracic nerve (T1) to conduct signals for motion and sensation throughout the arm. Brachial plexus birth injuries (BPBI) occur in 1.5 per 1,000 live births.

Connecting endoplasmic reticulum and oxidative stress to retinal degeneration, TBI, and traumatic optic neuropathy.

Traumatic optic neuropathy (TON) is commonly associated with head trauma, and thus is a known comorbidity of traumatic brain injury (TBI). TON has not received much attention in basic research despite being associated with permanent vision loss, color blindness, and loss of visual fields. This mini-review discusses the importance of studying TON in the context of TBI and mechanisms that may be involved in the ongoing optic nerve degeneration of TON.

Greater neurodegeneration and behavioral deficits after single closed head traumatic brain injury in adolescent versus adult male mice.

Traumatic brain injury (TBI) is a major public health concern affecting 2.8 million people per year in the United States, of whom about 1 million are children under 19 years old. Animal models of TBI have been developed and used in multiple ages of animals, but direct comparisons of adult and adolescent populations are rare.

Chronic Dysregulation of Cortical and Subcortical Metabolism After Experimental Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide. Although chronic disability is common after TBI, effective treatments remain elusive and chronic TBI pathophysiology is not well understood. Early after TBI, brain metabolism is disrupted due to unregulated ion release, mitochondrial damage, and interruption of molecular trafficking.

Optic tract injury after closed head traumatic brain injury in mice: A model of indirect traumatic optic neuropathy.

Adult male C57BL/6J mice have previously been reported to have motor and memory deficits after experimental closed head traumatic brain injury (TBI), without associated gross pathologic damage or neuroimaging changes detectable by magnetic resonance imaging or diffusion tensor imaging protocols. The presence of neurologic deficits, however, suggests neural damage or dysfunction in these animals. Accordingly, we undertook a histologic analysis of mice after TBI.

A Narrative Review of Pharmacologic and Non-pharmacologic Interventions for Disorders of Consciousness Following Brain Injury in the Pediatric Population.

Traumatic brain injury (TBI) is the most common cause of long-term disability in the United States. A significant proportion of children who experience a TBI will have moderate or severe injuries, which includes a period of decreased responsiveness. Both pharmacological and non-pharmacological modalities are used for treating disorders of consciousness after TBI in children.

Role of Paraventricular Nucleus Glutamate Signaling in Regulation of HPA Axis Stress Responses.

The hypothalamus-pituitary-adrenal (HPA) axis is the main neuroendocrine arm of the stress response, activation of which leads to the production of glucocorticoid hormones. Glucocorticoids are steroid hormones that are secreted from the adrenal cortex, and have a variety of effects on the body, including modulation of the immune system, suppression of reproductive hormones maintenance of blood glucose levels, and maintenance of blood pressure. Glutamate plays an important role in coordination of HPA axis output.

Metabotropic glutamate receptor-mediated signaling dampens the HPA axis response to restraint stress.

Glutamate is an important neurotransmitter in the regulation of the neural portion of hypothalamus-pituitary-adrenal (HPA) axis activity, and signals through ionotropic and metabotropic receptors. In the current studies we investigated the role of hypothalamic paraventricular group I metabotropic glutamate receptors in the regulation of the HPA axis response to restraint stress in rats. Direct injection of the group I metabotropic glutamate receptor agonist 3,5-dihydroxyphenylglycine (DHPG) into the PVN prior to restraint leads to blunting of the HPA axis response in awake animals.

Hydration state controls stress responsiveness and social behavior.

Life stress frequently occurs within the context of homeostatic challenge, requiring integration of physiological and psychological need into appropriate hormonal, cardiovascular, and behavioral responses. To test neural mechanisms underlying stress integration within the context of homeostatic adversity, we evaluated the impact of a pronounced physiological (hypernatremia) challenge on hypothalamic-pituitary-adrenal (HPA), cardiovascular, and behavioral responses to an acute psychogenic stress. Relative to normonatremic controls, rats rendered mildly hypernatremic had decreased HPA activation in response to physical restraint, a commonly used rodent model of psychogenic stress.

Pleasurable behaviors reduce stress via brain reward pathways.

Individuals often eat calorically dense, highly palatable "comfort" foods during stress for stress relief. This article demonstrates that palatable food intake (limited intake of sucrose drink) reduces neuroendocrine, cardiovascular, and behavioral responses to stress in rats. Artificially sweetened (saccharin) drink reproduces the stress dampening, whereas oral intragastric gavage of sucrose is without effect.

Fast feedback inhibition of the HPA axis by glucocorticoids is mediated by endocannabinoid signaling.

Glucocorticoid hormones are secreted in response to stimuli that activate the hypothalamo-pituitary-adrenocortical (HPA) axis and self-regulate through negative feedback. Negative feedback that occurs on a rapid time scale is thought to act through nongenomic mechanisms. In these studies, we investigated fast feedback inhibition of HPA axis stress responses by direct glucocorticoid action at the paraventricular nucleus of the hypothalamus (PVN).

GluR5-mediated glutamate signaling regulates hypothalamo-pituitary-adrenocortical stress responses at the paraventricular nucleus and median eminence.

Glutamate is the main excitatory neurotransmitter in the central nervous system, and plays an excitatory role in generation of hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. The current study assesses the role of kainate-preferring receptors in glutamatergic excitation of the HPA axis. In situ hybridization and immunohistochemical analyses confirmed the existence of the GluR5 kainate subunit in the paraventricular nucleus of the hypothalamus (PVN).

The role of the posterior medial bed nucleus of the stria terminalis in modulating hypothalamic-pituitary-adrenocortical axis responsiveness to acute and chronic stress.

The bed nucleus of the stria terminalis (BST) plays a prominent role in brain integration of acute responses to stressful stimuli. This study tests the hypothesis that the BST plays a complementary role in regulation of physiological changes associated with chronic stress exposure. Male Sprague-Dawley rats received bilateral ibotenate lesions or sham lesions of the posterior medial region of the BST (BSTpm), an area known to be involved in inhibition of HPA axis responses to acute stress.

The anteroventral bed nucleus of the stria terminalis differentially regulates hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress.

The anteroventral region of the bed nucleus of the stria terminalis (BST) stimulates hypothalamic-pituitary-adrenocortical (HPA) axis responses to acute stress. However, the role of the anterior BST nuclei in chronic drive of the HPA axis has yet to be established. Therefore, this study tests the role of the anteroventral BST in physiological responses to chronic drive, using a chronic variable stress (CVS) model.

Bed nucleus of the stria terminalis subregions differentially regulate hypothalamic-pituitary-adrenal axis activity: implications for the integration of limbic inputs.

Limbic and cortical neurocircuits profoundly influence hypothalamic-pituitary-adrenal (HPA) axis responses to stress yet have little or no direct projections to the hypothalamic paraventricular nucleus (PVN). Numerous lines of evidence suggest that the bed nucleus of the stria terminalis (BST) is well positioned to relay limbic information to the PVN. The BST comprises multiple anatomically distinct nuclei, of which some are known to receive direct limbic and/or cortical input and to heavily innervate the PVN.

Stability of neuroendocrine and behavioral responsiveness in aging Fischer 344/Brown-Norway hybrid rats.

Aging in rodents and primates is accompanied by changes in hypothalamic-pituitary-adrenal (HPA) activity. We examined behavioral and neuroendocrine responses in 3, 15-, and 30-month-old F344/Brown-Norway rats. Basal corticosterone and ACTH levels did not differ with age, although ACTH responses, but not corticosterone responses to restraint stress, were significantly lower in the 30-month-old group relative to 3- and 15-month-old rats.