Stroke is the 5th leading cause of death in the U.S. with 130,000 deaths and around 800,000 affected annually. Currently, there is a significant disconnect between basic stroke research and clinical stroke therapeutic needs. Few animal models of stroke target the large vessels that produce cortical deficits seen in the clinical setting. Also, current routes of drug administration, intraperitoneal and intravenous, do not mimic the clinical route of intra-arterial drug administration. To bridge this divide, we have retro-engineered a mouse model of stroke from the current standard of care for emergent large vessel occlusion (ELVO) stroke, endovascular thrombectomy, to include selective intra-arterial pharmacotherapy administration. Using the tandem transient common carotid and middle cerebral artery occlusion (MCAo) model to induce stroke, we threaded micro-angio tubing into the external carotid artery (ECA) towards the bifurcation of the common carotid and internal carotid arteries (CCA/ICA) allowing for the delivery of agents to the site of acute ischemia. Our model was optimized through a flow rate and injection volume study using carbon black ink injected through the intra-arterial model at different flow rates and injection volumes. The purpose of this study was to demonstrate that our injections were arriving at the site of ischemia and to improve injection volumes for future dosing while mitigating systemic side effects by preventing or minimizing systemic distribution. We determined that a flow rate of 2.5 µl/minute and injection volume of 10 µl was optimal. Next, we tested potential neuroprotective compounds nitroglycerin, verapamil, and a combination of verapamil and lubeluzole. Compounds were chosen for drug synergy and to target specific pathways in either an acute or delayed manner. Acute treatments included nitroglycerin and/or verapamil while delayed treatment included lubeluzole. The known mechanism of action for FDA approved nitroglycerin is through vessel dilation that results in increased blood flow to the treated region. A secondary mechanism of nitroglycerin is the production of nitric oxide, which has demonstrated antioxidant and anti-apoptotic effects when processed and released from cells surrounding the blood vessels. Verapamil, a calcium channel blocker, also FDA-approved for cerebral artery vasospasm: is thought to act by blocking the L-type calcium channels on the cell membrane from opening following membrane depolarization after insult. Finally, lubeluzole, also FDA-approved, is proposed to work as an NMDA modulator inhibiting the release of glutamate and nitric oxide synthase and blocking sodium and calcium channels. Through our stroke model we were able to demonstrate that each drug(s) showed a significant decrease in infarct volume and improved functional recovery while simultaneously minimizing potential systemic side effects suggesting that our stroke model may improve the preclinical validation of potential stroke therapies and help bridge the bench to bedside divide in developing new stroke therapies.

Background: Vestibular evoked myogenic potentials (VEMPs) have been recorded from the sternocleidomastoid muscle (cervical VEMP or cVEMP) and more recently from the eye muscles (ocular VEMP or oVEMP) in response to air conduction and bone conduction stimuli. Both cVEMPs and oVEMPs are mediated by the otoliths and thereby provide diagnostic information that is complementary to videonystagmography and rotational chair tests. In contrast to the air conduction cVEMP, which originates from the saccule/inferior vestibular nerve, recent evidence suggests the possibility that the air conduction oVEMP may be mediated by the utricle/superior vestibular nerve. The oVEMP, therefore, may provide complementary diagnostic information relative to the cVEMP. There are relatively few studies, however, that have quantified the effects of stimulus and recording parameters on the air conduction oVEMP, and there is a paucity of normative data. Purpose: To evaluate the effects of several stimulus and recording parameters on the air conduction oVEMP and to establish normative data for clinical use. Research Design: A prospective repeated measures design was utilized. Study Sample: Forty-seven young adults with no history of neurologic disease, hearing loss, middle ear pathology, open or closed head injury, cervical injury, or audiovestibular disorder participated in the study. Data Collection and Analysis: The effects of stimulus frequency, stimulus level, gaze elevation, and recording electrode location on the amplitude and latency of the oVEMP for monaural air conduction stimuli were assessed using repeated measures analyses of variance in an initial group of 17 participants. The optimal stimulus and recording parameters obtained in the initial group were used subsequently to obtain oVEMPs from 30 additional participants. Results: The effects of stimulus frequency, stimulus level, gaze elevation, and electrode location on the response prevalence, amplitude, and latency of the oVEMP for monaural air conduction stimuli were significant. The maximum N1-P1 amplitude and response prevalence were obtained for contralateral oVEMPs using a 500 Hz tone burst presented at 125 dB peak SPL during upward gaze at an elevation of 30°. Conclusions: The optimal stimulus and recording parameters quantified in this study were used to establish normative data that may be useful for the clinical application of the air conduction oVEMP.

Background: The otoliths act as gravito-inertial force sensors and contribute to the perception of spatial orientation. The perception of gravitational vertical can be assessed by asking a subject to adjust a light bar to the vertical. Prior to clinical use of the SVV (subjective visual vertical) test, normative data and test-retest reliability must be established. Purpose: To obtain normative data and d etermine the test-retest reliability for the SVV test performed in static and dynamic test conditions. Research Design: A descriptive design was used to obtain normative data. Study Sample: Twenty-four young adults with no history of neurological disease, middle-ear pathology, open or closed head injury, cervical injury, or audiovestibular disorder participated in the study. Data Collection and Analysis: The SVV angle was measured in the static position and in three dynamic conditions: (1) on-axis clockwise (CW) rotation, (2) off-axis CW rotation of right ear, and (3) off-axis CW rotation of left ear. Results: In young healthy individuals, the SVV was Conclusions: The normative data obtained in this study may be useful in identifying patients with chronic utricular dysfunction. We recommend the use of difference angles (on-axis SVV ‐ off-axis SVV) to remove baseline bias and decrease the variability of the SVV angles for the off-axis conditions.

Medial tibial stress syndrome (MTSS) is a stress and overuse injury that presents as pain on the medial aspect of the lower two-thirds of the tibia. It is most often caused by repetitive actions on hard surfaces such as running, marching, and dancing. Individuals most affected by MTSS are runners, members of the military, dancers, and athletes that play soccer, volleyball and basketball. While MTSS has a relatively standard presentation of pain on the medial aspect of the tibia, it can occasionally be mistaken for other injuries such as stress fractures or compartment syndrome. If a diagnosis is unsure, methods such as x-ray, bone-scan, and MRI can be utilized to better obtain the correct diagnosis. A variety of treatments exist for MTSS including, ice, massage, muscle strengthening, and rest. A combination of these various techniques is most often what is employed. In this study, the effectiveness of a set of resistance ankle exercises in combination with ice and massage was tested and compared to that of ice and massage alone. The hypothesis was that athletes receiving the exercises as part of their treatment, in addition to the icing and massaging, would have a greater decrease in pain from MTSS than athletes just receiving ice and massage as treatment. The exercises would strengthen the muscles of the lower leg that, when weak, can contribute to the development of MTSS. Results indicated that the exercises yielded a more significant decrease in pain from MTSS than ice and massage alone.

Huntington’s disease is an incurable, progressive neurological disorder characterized by loss of motor control, psychiatric dysfunction, and eventual dystonia leading to death. Despite the fact that this disorder is caused by a mutation in one single gene, there is no cure. The mutant Huntingtin (mHtt) protein is expressed ubiquitously throughout the brain but frank cell death is limited to the striatum. Recent work has suggested that Rhes, Ras homolog enriched in striatum, which is selectively expressed in the striatum, may play a role in Huntington’s disease neuropathology. In vitro studies have shown Rhes to be an E3 ligase for the post-translational modification protein SUMO. Rhes increases binding of SUMO to mHtt which competes for the same binding site as Ubiquitin. SUMOylation of mHtt leads to disaggregation and cellular death, whereas ubiquitination leads to aggregation and cellular protection. In a previous study we showed that deletion of Rhes caused a decrease in the Huntington’s disease phenotype in mice. We hypothesized that mice lacking Rhes would also show increased aggregation in the striatum and this increased aggregation would correlate in a rescue of behavioral symptoms. Despite the prior in vitro and in vivo evidence, deletion of Rhes in vivo did not alter the aggregation of mHtt in the striatum of mice however deletion of Rhes still showed a rescue from the diseased phenotype. This result would indicate that deletion of Rhes alters the neurobehavioral phenotype of Huntington’s disease through a different pathway than promoting aggregation in striatal cells.

The purpose of this article is to review relevant literature on the effect of mild traumatic brain injury (mTBI) and blast injury on the vestibular system. Dizziness and imbalance are common sequelae associated with mTBI, and in some individuals, these symptoms may last for six months or longer. In war-related injuries, mTBI is often associated with blast exposure. The causes of dizziness or imbalance following mTBI and blast injuries have been linked to white matter abnormalities, diffuse axonal injury in the brain, and central and peripheral vestibular system damage. There is some evidence that the otolith organs may be more vulnerable to damage from blast exposure or mTBI than the horizontal semicircular canals. In addition, benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder following head injury that is treated effectively with canalith repositioning therapy. Treatment for (non-BPPV) mTBI-related vestibular dysfunction has focused on the use of vestibular rehabilitation (VR) augmented with additional rehabilitation methods and medication. New treatment approaches may be necessary for effective otolith organ pathway recovery in addition to traditional VR for horizontal semicircular canal (vestibulo-ocular reflex) recovery.

Objective: Cervical vestibular evoked myogenic potentials (cVEMPs) are short-latency electromyogram (EMG) evoked by high-level acoustic stimuli recorded from the activated sternocleidomastoid muscle and used to evaluate otolith organ function. The purpose of this study was to investigate the effects of aging on the cVEMP and on the sternocleidomastoid muscle EMG level. Design: A cross-sectional observational study was used to investigate differences in cVEMP and sternocleidomastoid muscle EMG level in a group of 24 younger and 24 older individuals. cVEMPs were recorded during activation of the sternocleidomastoid muscle at target EMG levels ranging from 0 to 90 μV and during maximum voluntary contraction of the sternocleidomastoid muscle. Results: The sternocleidomastoid muscle EMG amplitude increased as a function of target EMG level for both age groups; however, the mean EMG amplitude was greater for the younger group than the older group, and the variability of EMG amplitude was greater for the older group. The EMG amplitude at maximum voluntary contraction ranged from 88 to 279 μV for the younger subjects and from 32 to 230 μV for the older subjects, and the mean EMG amplitude at maximum voluntary contraction was significantly greater for the younger group than the older group. The cVEMP amplitude increased as a function of EMG target level for each age group. Although cVEMP amplitude increased as a function of target EMG level for both groups, the older group exhibited smaller cVEMP amplitudes, overall, compared with the younger group. To separate the influence of EMG level from aging on cVEMP amplitude, only the responses obtained at the 30 μV target EMG level were considered for the statistical analysis because there was no significant difference in EMG level between groups at the 30 μV target level. The mean cVEMP amplitudes at the 30 μV target level were 101 and 51 μV for the younger and older groups, respectively, and a statistical analysis indicated that cVEMP amplitude for the younger group was significantly greater than the older group. Conclusions: The findings suggest that the decrement in cVEMP amplitude is related to both age-related changes in the vestibular system and age-related changes in the sternocleidomastoid muscle.

Autism spectrum disorders (ASD) encompass neurodevelopment disorders characterized by atypical patterns of development that impact multiple areas of functioning beginning in early childhood. The etiology of ASD is unknown and there are currently no preventative treatment options. Gastrointestinal symptoms are commonly associated comorbidities. The microbiota-gut-brain axis is a multidirectional communication chain that connects the central and enteric nervous system that relates brain function to peripheral intestinal functions. Changes within this axis have been postulated in ASD. For example, the “leaky gut theory” proposes that chronic inflammation is linked to alterations in the bacterial profiles of the gut microbiome and subsequent shifts in the amount and type of short-chain fatty acids produced can affect downstream neuronal development. Short-chain fatty acids are signaling molecules produced by bacteria that can trigger nerve afferents in the gut. Dysbiosis causes altered signaling patterns that can be identified by altered intestinal morphology. In this study, C57BL/6J control mice and three mouse models of social behavioral deficits were used to investigate markers of intestinal pathophysiology. Fecal and intestinal samples were collected from adult wild type control mice and the social deficit groups of BTBR genetic knockout mice, C57BL/6J mice injected with valproic acid, and C57BL/6J mice injected with polyinosinic–polycytidylic acid. Short-chain fatty acid profiles that included acetic, propionic, isobutyric, butyric, isovaleric, and valeric acids were obtained from fecal samples to determine differences between the models and control mice. The profiles of the BTBR genetic knockout and valproic acid models were found to be significantly different from control mice. Additionally, postmortem intestinal ileum samples underwent hematoxylin and eosin identification procedures to determine the thickness of the tunica muscularis and tunica mucosa. The thickness of the tunica muscularis was reduced in the valproic acid group compared to the wild type control mice in early stages of development (p=0.0279). This research may illuminate developmental cues that attribute to autism spectrum disorders and may provide markers to assess future therapeutic treatments.

Winged scapula is a condition characterized by lateral or medial protrusion of the scapula caused by nerve damage leading to muscular paralysis. The purpose of this systematic review of literature is to evaluate the current research literature related to the effectiveness of therapy options for winged scapula. Eleven peer reviewed English language research articles published from 1998 to present were included for evaluation. Study results revealed positive therapeutic outcomes for physical therapy and scapular bracing. Results also showed positive outcomes for the use of transcutaneous electrical nerve stimulation and acupuncture for the treatment of nerve related conditions similar to winged scapula. Additional research is needed to evaluate the effectiveness of transcutaneous electrical nerve stimulation and acupuncture for winged scapula patients specifically.

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological response to cold exposure and endothelial function encourage further study of the effects of ice plunging on cardiovascular health. Calibrated cuff plethysmography is a promising method of reflecting on endothelial function by measuring arterial compliance of select blood vessels. In this study, a calibrated cuff plethysmography device was built and tested for efficiency as it was used to measure compliance and cross-sectional area of the brachial artery of 14 participants 30 minutes before, immediately after, and 30 minutes after a 5-minute cold plunge in a temperature of 10°C - 15°C. Results found some significant differences between baseline measurements recorded immediately after the ice plunge and measurements recorded during reactive hyperemia conditions at normal body temperature but did not conclude that 5-minute cold-water immersion intervention had a significant impact on arterial compliance or area overall since this was a short term experiment with only acute intervention methods. The device used was concluded to effectively measure arterial compliance and area.