Sex-specific Stone-forming Phenotype in Mice During Hypercalciuria/Urine Alkalinization.

Sex differences in kidney stone formation are well known. Females generally have slightly acidic blood and higher urine pH when compared with males, which makes them more vulnerable to calcium stone formation, yet the mechanism is still unclear. We aimed to examine the role of sex in stone formation during hypercalciuria and urine alkalinization through acetazolamide and calcium gluconate supplementation, respectively, for 4 weeks in wild-type (WT) and moderately hypercalciuric [TRPC3 knockout [KO](-/-)] male and female mice. Our goal was to develop calcium phosphate (CaP) and CaP+ calcium oxalate mixed stones in our animal model to understand the underlying sex-based mechanism of calcium nephrolithiasis. Our results from the analyses of mice urine, serum, and kidney tissues show that female mice (WT and KO) produce more urinary CaP crystals, higher [Ca2+], and pH in urine compared to their male counterparts. We identified a sex-based relationship of stone-forming phenotypes (types of stones) in our mice model following urine alkalization/calcium supplementation, and our findings suggest that female mice are more susceptible to CaP stones under those conditions. Calcification and fibrotic and inflammatory markers were elevated in treated female mice compared with their male counterparts, and more so in TRPC3 KO mice compared with their WT counterparts. Together these findings contribute to a mechanistic understanding of sex-influenced CaP and mixed stone formation that can be used as a basis for determining the factors in sex-related clinical studies.

Inhalational Gases for Neuroprotection in Traumatic Brain Injury.

Despite multiple prior pharmacological trials in traumatic brain injury (TBI), the search for an effective, safe, and practical treatment of these patients remains ongoing. Given the ease of delivery and rapid absorption into the systemic circulation, inhalational gases that have neuroprotective properties will be an invaluable resource in the clinical management of TBI patients. In this review, we perform a systematic review of both pre-clinical and clinical reports describing inhalational gas therapy in the setting of TBI. Hyperbaric oxygen, which has been investigated for many years, and some of the newest developments are reviewed. Also, promising new therapies such as hydrogen gas, hydrogen sulfide gas, and nitric oxide are discussed. Moreover, novel therapies such as xenon and argon gases and delivery methods using microbubbles are explored.

Radiosurgical Thalamotomy.

Tremor is a common movement disorder that can be disabling, and its initial treatment is in the form of medical therapies. Often patients are refractory and seek surgical intervention. Treatment options for these patients include surgical radiofrequency thalamotomy and deep brain stimulation. There are a subset of patients who, for various reasons, are not candidates for open surgical procedures, or who opt to avoid them. For these patients, radiosurgical thalamotomy is a safe and useful alternative. Herein, we provide a review of the use of radiosurgical thalamotomy for the treatment of medically refractory tremor by discussing its history, defining the technique and its indications, evaluating its efficacy, and exploring its complications and shortcomings.

Neurostimulation for traumatic brain injury.

Traumatic brain injury (TBI) remains a significant public health problem and is a leading cause of death and disability in many countries. Durable treatments for neurological function deficits following TBI have been elusive, as there are currently no FDA-approved therapeutic modalities for mitigating the consequences of TBI. Neurostimulation strategies using various forms of electrical stimulation have recently been applied to treat functional deficits in animal models and clinical stroke trials. The results from these studies suggest that neurostimulation may augment improvements in both motor and cognitive deficits after brain injury. Several studies have taken this approach in animal models of TBI, showing both behavioral enhancement and biological evidence of recovery. There have been only a few studies using deep brain stimulation (DBS) in human TBI patients, and future studies are warranted to validate the feasibility of this technique in the clinical treatment of TBI. In this review, the authors summarize insights from studies employing neurostimulation techniques in the setting of brain injury. Moreover, they relate these findings to the future prospect of using DBS to ameliorate motor and cognitive deficits following TBI.

Oral fish oil restores striatal dopamine release after traumatic brain injury.

Omega-3 fatty acid administration can affect the release of neurotransmitters and reduce inflammation and oxidative stress, but its use in traumatic brain injury (TBI) has not been described extensively. We investigated the effect of 7 day oral fish oil treatment in the recovery of potassium evoked dopamine release after TBI. Sham rats and TBI rats were given either olive oil or fish oil by oral gavage and were subject to cerebral microdialysis. Olive oil treated TBI rats showed significant dopamine release deficit compared to sham rats, and this deficit was restored with oral fish oil treatment. There was no effect of fish oil treatment on extracellular levels of dopamine metabolites such as 3,4-dihydroxyphenylacetic acid and homovanillic acid. These results suggest the therapeutic potential of omega-3 fatty acids in restoring dopamine neurotransmission deficits after TBI.