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Introduction
Additional affiliations
July 2019 - present
May 2010 - January 2014
July 2017 - April 2018
Education
August 2006 - April 2010
August 2004 - August 2006
September 1999 - May 2003
Publications
Publications (65)
Recent studies have reported that TBI is an independent risk factor for subsequent stroke. Here, we tested the hypothesis that TBI would exacerbate experimental stroke outcomes via alternations in neuroimmune and neurometabolic function. We performed a mild closed-head TBI and then one week later induced an experimental stroke in adult male mice. M...
Physician prescribed rest after traumatic brain injury (TBI) is both commonplace and an increasingly scrutinized approach to TBI treatment. Although this practice remains a standard of patient care for TBI, research of patient outcomes reveals little to no benefit of prescribed rest after TBI, and in some cases prolonged rest has been shown to inte...
Traumatic brain injuries (TBI) are a significant public health problem costing billions of dollars in healthcare costs and lost productivity while simultaneously reducing the quality of life for both patients and caregivers. Substance abuse is closely interconnected with TBI, as intoxicated individuals are at a greater risk of suffering brain injur...
Intoxication is a leading risk factor for injury, and TBI increases the risk for later alcohol misuse, especially when the injury is sustained in childhood. Previously, we modeled this pattern in mice, wherein females injured at postnatal day 21 drank significantly more than uninjured females, while we did not see this effect in males. However, the...
Traumatic brain injury (TBI) represents a major public health concern. Although the majority of individuals that suffer mild-moderate TBI recover relatively quickly, a substantial subset of individuals experiences prolonged and debilitating symptoms. An exacerbated response to physiological and psychological stressors after TBI may mediate poor fun...
Growing evidence supports that early- or middle-life traumatic brain injury (TBI) is a risk factor for developing Alzheimer’s disease (AD) and AD-related dementia (ADRD). Nevertheless, the molecular mechanisms underlying TBI-induced AD-like pathology and cognitive deficits remain unclear. In this study, we found that a single TBI (induced by contro...
Background: The hippocampus and cortex are susceptible to changes in blood supply, metabolites, and oxygenation. However, how disrupted cardiac function affects these critical areas of the brain, leading to the cognitive and neurological consequences of heart failure, remains unclear.
Hypothesis: We hypothesize that disrupted cardiac function cross...
Mild-moderate traumatic brain injuries (TBIs) are prevalent, and while many individuals recover, there is evidence that a significant number experience long-term health impacts, including increased vulnerability to neurodegenerative diseases. These effects are influenced by other risk factors, such as cardiovascular disease. Our study tested the hy...
Pericytes are critical yet understudied cells that are a central component of the neurovascular unit. They are connected to the cerebrovascular endothelium and help control vascular contractility and maintain the blood–brain barrier. Pericyte dysfunction has the potential to mediate many of the deleterious vascular consequences of ischemic stroke....
Physical exercise represents a potentially inexpensive, accessible, and optimizable rehabilitation approach to traumatic brain injury (TBI) recovery. However, little is known about the impact of post-injury exercise on the neurometabolic, transcriptional, and cognitive outcomes following a TBI. In the current study, we examined TBI outcomes in adol...
Alzheimer disease (AD) and traumatic brain injury (TBI) are two devastating brain disorders with complex relationships. Growing evidence supports that early or middle life of TBI may be a risk factor for developing late‐life AD and AD‐related dementias (ADRD). Tau hyperphosphorylation and gliosis may serve as a causative link between TBI and AD as...
Mild traumatic brain injury (mTBI) produces subtle cerebrovascular impairments that persist over time and promote increased ischemic stroke vulnerability. We recently established a role for vascular impairments in exacerbating stroke outcomes one week after TBI, but there is a lack of research regarding long-term impacts of mTBI-induced vascular dy...
Rest after traumatic brain injury (TBI) has been a part of clinical practice for more than a century but the use of rest as a treatment has ancient roots. In contemporary practice, rest recommendations have been significantly reduced but are still present. This advice to brain injured patients, on the face of it makes some logical sense but was not...
Traumatic brain injuries in children represent a major public health issue and even relatively mild injuries can have lifelong consequences. However, the outcomes from these injuries are highly heterogeneous, with most individuals recovering fully, but a substantial subset experiencing prolonged or permanent disabilities across a number of domains....
Traumatic brain injury (TBI) is closely interrelated with alcohol use disorders. This is mediated, in part, by the large number of individuals who are intoxicated at the time of their injuries. However, there is also evidence, both preclinically and epidemiologically that TBI, particularly when it occurs early in life can increase the incidence of...
Alcohol use and traumatic brain injury (TBI) are inextricably and bidirectionally linked. Alcohol intoxication is one of the strongest predictors of TBI, and a substantial proportion of TBIs occur in intoxicated individuals. An inverse relationship is also emerging, such that TBI can serve as a risk factor for, or modulate the course of, alcohol us...
Alcohol use is a well characterized risk factor for traumatic brain injury (TBI); however, emerging clinical and experimental research suggests that TBI may also be an independent risk factor for the development of alcohol use disorders. In particular, TBIs incurred early in life predict the development of problem alcohol use and increase vulnerabi...
Traumatic brain injuries (TBI) are a common and costly ongoing public health concern. Injuries that occur during childhood development can have particularly profound and long-lasting effects. One common consequence and potential mediator of negative outcomes of TBI is sleep disruption which occurs in a substantial proportion of TBI patients. These...
Mitogen-activated protein kinase (MAPK) signaling has been implicated in a wide range of neuronal processes, including development, plasticity, and viability. One of the principal downstream targets of both the extracellular signal-regulated kinase/MAPK pathway and the p38 MAPK pathway is Mitogen- and Stress-activated protein Kinase 1 (MSK1). Here,...
Traumatic brain injuries (TBI) sustained during peri-adolescent development produce lasting neuro-behavioral changes that render individuals at an increased risk for developing substance abuse disorders. Experimental and clinical evidence of a prolonged period of hypodopaminergia after TBI have been well documented, but the effect of juvenile TBI o...
Traumatic brain injuries are strongly related to alcohol intoxication as by some estimates
half or more of all brain injuries involve at least one intoxicated individual. Additionally,
there is mounting evidence that traumatic brain injuries can themselves serve as
independent risk factors for the development of alcohol use disorders, particularly...
Traumatic brain injuries (TBI) are a major public health problem with enormous costs in terms of health care dollars, lost productivity, and reduced quality of life. Alcohol is bidirectionally linked to TBI as many TBI patients are intoxicated at the time of their injury and we recently reported that, in accordance with human epidemiological data,...
Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the contribut...
A subset of traumatic brain injury (TBI) patients exhibit cognitive deficits later in life which may be due to the underlying pathology associated with Alzheimer's disease (AD) or chronic traumatic encephalopathy. The similarities between chronic traumatic encephalopathy and AD merit investigation of potentially similar mechanisms underlying the tw...
Traumatic brain injury (TBI) is inextricably and bidirectionally linked with alcohol use, as by some estimates intoxication is the direct or indirect cause of one-third to one-half of all TBI cases. Alcohol use following injury can reduce the efficacy of rehabilitation and increase the chances for additional injury. Finally, TBI itself may be a ris...
Head injuries are a major public health concern for youth and adult athletes, members of the police and armed forces and the general public. In the US alone, each year approximately 1.4 million people
are hospitalized with a traumatic brain injury. There is an innate conflict between an institutional desire to return individuals to the playing fiel...
Pathophysiological conditions such as cerebral ischemia trigger the production of new neurons from the neurogenic niche within the subgranular zone (SGZ) of the dentate gyrus. The functional significance of ischemia-induced neurogenesis is believed to be the regeneration of lost cells, thus contributing to post-ischemia recovery. However, the cell...
In previous laboratory investigations, we have identified enhanced cognition and reduced stress in parous rats, which are likely adaptations in mothers needing to efficiently exploit resources to maintain, protect and provision their immature offspring. Here, in a series of seven behavioral tests on rats, we examined a natural interface between cog...
Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and...
Cerebral ischemia induces a complex interplay of events that contribute to both the pathophysiology and partial recovery of the affected tissue. Within hours of an ischemic event, a convergence of neuroinflammation, oxidative stress, and high levels of excitatory neuortransmission lead to cell injury and ultimately cell death. Concurrently, cerebra...
The master circadian clock in mammals, the suprachiasmatic nucleus (SCN), is under the entraining influence of the external light cycle. At a mechanistic level, intracellular signaling via the p42/44 mitogen-activated protein kinase pathway appears to play a central role in light-evoked clock entrainment; however, the precise downstream mechanisms...
Environmental enrichment (EE) has marked beneficial effects on cognitive capacity. Given the possibility that this form of neuronal plasticity could function via the actuation of the same cellular signaling pathways that underlie learning/memory formation, we examined whether the MAPK cascade effector, mitogen/stress-activated kinase 1 (MSK1), coul...
The neurogenic niche within the subgranular zone (SGZ) of the dentate gyrus is a source of new neurons throughout life. Interestingly, SGZ proliferative capacity is regulated by both physiological and pathophysiological conditions. One outstanding question involves the molecular mechanisms that regulate both basal and inducible adult neurogenesis....
Within the central nervous system, microRNAs have emerged as important effectors of an array of developmental, physiological, and cognitive processes. Along these lines, the CREB-regulated microRNA miR-132 has been shown to influence neuronal maturation via its effects on dendritic arborization and spinogenesis. In the mature nervous system, dysreg...
This study examines the relationship between autonomic functioning and neuropathology following cardiac arrest (CA) in mice. Within 24 h of CA, parasympathetic cardiac control, as indexed by high frequency (HF) heart rate variability, rapidly decreases. By day 7 after CA, HF heart rate variability was inversely correlated with neuronal damage and m...
The reduced incidence, morbidity, and mortality of stroke among humans with strong social support have been well-documented; however, the mechanisms underlying these socially mediated phenomena remain unknown, but may involve oxytocin (OT), a hormone that modulates some aspects of social behavior in humans and other animals.
In the present study, a...
This study examined the photoperiodic regulation of energy balance and cannabinoid receptor expression in the Siberian hamster (Phodopus sungorus) hypothalamus. Short day lengths, beginning at weaning, reduced food intake, body mass and fat pad masses and also decreased cannabinoid receptor immunostaining in the anterior and lateral hypothalamic nu...
Cardiac arrest is a leading cause of death worldwide. While survival rates following sudden cardiac arrest remain relatively low, recent advancements in patient care have begun to increase the proportion of individuals who survive cardiac arrest. However, many of these individuals subsequently develop physiological and psychiatric conditions that l...
Social interactions have long-term physiological, psychological, and behavioral consequences. Social isolation is a well-recognized but little understood risk factor and prognostic marker of disease; it can have profoundly detrimental effects on both mental and physical well-being, particularly during states of compromised health. In contrast, the...
J. Neurochem. (2011) 116, 1–9.
Since its initial characterization over 20 years ago, there has been intense and unwavering interest in understanding the role of the transcription factor cAMP-responsive element binding protein (CREB) in nervous system physiology. Through an array of experimental approaches and model systems, researchers have begun t...
Psychological factors, including depression and social isolation, are important determinants of cardiovascular health. The current study uses a well-validated mouse model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR) to examine the effect of social environment on several pathophysiological and behavioral responses to cerebral ischemia. M...
To examine the salubrious role of social interaction in modulating the development of allodynia (increased sensitivity to typically innocuous physical stimuli) and depressive-like behavior post peripheral nerve injury in mice. The determination of potential mechanisms that mediate social influences on the behavioral and physiological response to pe...
The neuropeptide oxytocin has been implicated in a wide range of social processes, such as pair bonding, affiliation, and social judgments that may contribute to normal adjustment and psychiatric states. The present experimental study sought to elucidate potential underlying mechanisms by which oxytocin may impact social processes by examining the...
The social organization of rodent species determines behavioral patterns for both affiliative and agonistic encounters. The neuropeptide oxytocin has been implicated in the mediation of social behavior; however, variability in both neuropeptide expression and social behavior within a single species indicates an additional mediating factor. The purp...
Social interaction is neuroprotective following stroke, however, social housing introduces numerous social and sensory stimuli, and the individual contribution of these stimuli to stroke outcome is unknown. The current study was designed to investigate the role of physical contact in mediating the protective effect of social interaction in a rodent...
The present work examines the relationship between reproductive experience (comprising breeding, parturition, and lactation) and the behavioral and hormonal processes of fear and stress in the female laboratory rat. Previous research has indicated that reproductive experience functions to decrease the female's stress response in potentially harmful...
Ischemic events in humans are not evenly distributed across the day. To discriminate between temporal differences in the incidence of ischemia and susceptibility to ischemic events, we examined the outcome of global ischemia in a murine model at three time points during the day. Global cerebral ischemia in mice during the light phase impairs surviv...
Stress is an important risk factor for cardiovascular disease; however, most of the research on this topic has focused on incidence rather than outcome. The goal of this study was to determine the effects of prior exposure to chronic stress on ischemia-induced neuronal death, microglial activation, and anxiety-like behavior.
In Experiment 1, mice w...
The physiological link between neuropathic pain and depression remains unknown despite a high comorbidity between these two disorders. A mouse model of spared nerve injury (SNI) was used to test the hypothesis that nerve injury precipitates depression through the induction of inflammation in the brain, and that prior exposure to stress exacerbates...
Although the biological function of sleep remains uncertain, the consequences of sleep deprivation are well-described and are reported to be detrimental to cognitive function and affective well-being. Sleep deprivation also is strongly associated with elevated risk factors for cardiovascular disease. We used a mouse model of cardiac arrest/cardiopu...
WIN-55,212-2 (WIN-2) can elicit anti-inflammatory and cognitive-enhancing effect in aged rats. The current study was designed to determine the differential role of the endocannabinoid receptor sub-types 1 (CB1) and 2 (CB2) and transient receptor potential vanilloid 1 receptor (TRPV1) in the reduction of age-associated brain inflammation and their e...
Cardiac arrest and cardiopulmonary resuscitation (CA/CPR) increase the risk for affective disorders in human survivors. Postischemic anxiety- and depressive-like behaviors have been documented in animal models of CA/CPR; however, the stability of post-CA/CPR anxiety-like behavior over time and the underlying physiologic mechanisms remain unknown. T...
Social isolation has dramatic long-term physiological and psychological consequences; however, the mechanisms by which social isolation influences disease outcome are largely unknown. The purpose of the present study was to investigate the effects of social isolation on neuronal damage, neuroinflammation, and functional outcome after focal cerebral...
The detection of salient or instrumental stimuli and the selection of cue-evoked responses are mediated by a fronto-parietal network that is modulated by cholinergic inputs originating from the basal forebrain. Visual cues that guide behavior are more strongly represented in the posterior parietal cortex (PPC) than are similar cues that are missed...
Maternal behavior is multidimensional, encompassing many facets beyond the direct care of the young. Formerly unfamiliar activities are required of the mother. These include behaviors such as retrieving, grouping, crouching-over, and licking young, and protecting them against predators, together with enhancements in other behaviors, such as nest bu...
Questions
Questions (4)
Does anyone have a protocol for neonatal gonadectomy for mice (both sexes)?
I ran a novel object recognition test on mice that underwent traumatic brain injury (or sham) and were treated with a drug (or vehicle). My sham controls (both treated and untreated) performed well and showed clear preference for the novel object (>60%), the TBI untreated group exhibited no preference for the novel object. Curiously, the drug treated TBI group exhibited a pretty strong avoidance of the novel object, only actively investigating it about 25% of the time. Does anyone with experience in this task have some insight into how to interpret this result? Is it neophobia? Anxiety?
I am working with a dopamine transporter antibody for western blotting and it gives two bands: 50kDa for the reduced form and 80kDa for the non-reduced form. I was wondering if anyone could shed light on what these distinctions refer to?
I've been having a problem with my samples not stacking well during SDS-PAGE. I'm following a protocol that has worked very well for the past year or so and is for some reason having issues now. I use bio-rad precast gels (#456-1086), I load 40ug sample and run at 80V, then increase to 120V. I have checked the buffer pH and make it fresh each time. I've tried buying new gels. The attached picture is representative of what it looks like, the samples run that way all the way down the gel, they never stack properly. I appreciate any suggestions!
