Field Neurosciences Institute

Background: Patients with traumatic brain injury (TBI) are at elevated risk for forming venous thromboembolism (VTE), warranting initiation of VTE chemoprophylaxis as early as possible, though the timing of initiation is unclear, particularly when intracranial hemorrhage (ICH) is also present. The purpose of this study is to evaluate the safety of early initiation of chemoprophylaxis in the TBI patient population with ICH on initial imaging.Methods: A 2-year retrospective cohort study was conducted on eligible trauma patients admitted to MyMichigan Medical Center Saginaw who sustained ICH and received subcutaneous heparin (SQH) prophylaxis within 24 h of the first stable head computed tomography (CTH). The primary outcome of interest was the change in hemorrhage size on subsequent CTHs following SQH initiation.Results: 63 patients met the inclusion criteria. On the first imaging post-SQ heparin initiation, 26 of the 63 patients (41%) had improved ICH, 37 patients (59%) had stable ICH, and none had worsening ICH.Conclusion: In TBI patients with ICH, administration of SQH chemoprophylaxis within the first 24 h of stable imaging appears to be safe, without the risk of worsening hemorrhage.

To catalog and correlate the clinical features and mutational spectrum of neurofibromatosis type 1 (NF1) patients attending a tertiary care center in India. NF1 patients with confirmed molecular diagnosis from 2014 to 2021 were included in the study. The molecular tests used for the diagnosis were exome sequencing, targeted gene sequencing, and Multiple Ligation Probe Assay. Forty-two clinically diagnosed NF1 patients who had confirmed molecular diagnosis, which is now part of the revised diagnostic criteria, were included in the analysis. Nonsense variants were the most frequently observed (35.71%), followed by frameshift (23.8%), splice site (14.29%), deletion (11.9%), missense (9.5%), and in-frame deletions (4.76%) in our case series. Three variants (c. 5269-1G > C, c. 1541_1542del AG, and c. 6853_6854insA) were identified in more than one patient, suggesting that the variants are widely distributed in the gene and lack any mutational hotspot. This study supports the previous findings that patients with the variant c. 2970_2972delAAT do not develop neurofibromas; however, it was not necessary for those with whole gene deletion to have dysmorphic features as reported by other studies. The study could not establish any correlation between the type of variants and specific clinical features. Around 28% of mutations could be identified by screening exons 14, 28, 37, 46 and intron 37 in this population. This study will contribute to a better understanding of the phenotypic variability of neurofibromatosis patients. The variable expressivity seen in NF1 suggests that modifying genes may be involved in the development of particular clinical features in addition to NF1 mutations.

Aging-induced proteinopathies, including deterioration of amyloid beta (Aβ) conformation, are associated with reductions in endogenous levels of carnosine and cognitive impairments. Carnosine is a well-known endogenous antioxidant, which counteracts aging-induced Aβ plaque formation. The aim of this study was to investigate the effects of exogenous carnosine treatments on aging-induced changes (a) in the steady-state level of endogenous carnosine and conformation of Aβ secondary structure in the different brain regions (cerebral cortex, hippocampus, hypothalamus, pons-medulla, and cerebellum) and (b) cognitive function. Young (4months) and aged (18 and 24months) male albino Wistar rats were treated with carnosine (2.0μgkg-1 day-1 ; i.t.) or equivalent volumes of vehicle (saline) for 21 consecutive days and were tested for cognition using 8-arm radial maze test. Brains were processed to assess the conformational integrity of Aβ plaques using Raman spectroscopy and endogenous levels of carnosine were measured in the brain regions using HPLC. Results indicated that carnosine treatments improved the aging-induced deficits in cognitive function and reduced the β-sheets in the secondary structure of Aβ protein, as well as mitigating the reduction in the steady-state levels of carnosine and spine density in the brain regions examined. These results thus, suggest that carnosine can attenuate the aging-induced: (a) conformational changes in Aβ secondary structure by reducing the abundance of β-sheets and reductions in carnosine content in the brain regions and (b) cognitive impairment.

Polyamidoamine (PAMAM) dendrimers are one of the smallest and most precise nanomolecules available today, which have promising applications for the treatment of brain diseases. Each aspect of the dendrimer (core, size or generation, size of cavities, and surface functional groups) can be precisely modulated to yield a variety of nanocarriers for delivery of drugs and genes to brain cells in vitro or in vivo. Two of the most important criteria to consider when using PAMAM dendrimers for neuroscience applications is their safety profile and their potential to be prepared in a reproducible manner. Based on these criteria, features of PAMAM dendrimers are described to help the neuroscience researcher to judiciously choose the right type of dendrimer and the appropriate method for loading the drug to form a safe and effective delivery system to the brain.

Aggregation of amyloid beta protein (Aβ) and phosphorylated tau (p-Tau) plays critical roles in pathogenesis of Alzheimer's disease (AD). As an antiamyloid natural polyphenol, curcumin (Cur) has a potential role in prevention of neurodegeneration in AD. However, due to limited absorption of the dietary Cur, the solid lipid Cur particles (SLCP) have been suggested as being more effective for AD therapy. In the present study, we compared the role of dietary Cur and SLCP on oxidative stress, neuronal death, p-Tau level, and certain cell survival markers in vitro, after exposure to Aβ42. Mouse neuroblastoma cells were exposed to Aβ42 for 24 h and incubated with or without dietary Cur and/or SLCP. Reactive oxygen species (ROS), apoptotic cell death, p-Tau, and tau kinase (including GSK-3β and cell survival markers, such as total Akt, phosphorylated Akt, and PSD95 levels) were investigated. SLCP showed greater permeability than dietary Cur in vitro, decreased ROS production, and prevented apoptotic death. In addition, SLCP also inhibited p-Tau formation and significantly decreased GSK-3β levels. Further, the cell survival markers, such as total Akt, p-Akt, and PSD95 levels, were more effectively maintained by SLCP than dietary Cur in Aβ42 exposed cells. Therefore, SLCP may provide greater neuroprotection than dietary Cur in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by a progressive loss of memory and other cognitive disturbances. The neuropathology of AD includes the major hallmarks of toxic amyloid-β oligomer accumulation and neurofibrillary tangles, as well as increased oxidative stress, cholinergic dysfunction, synapse loss, changes in endogenous neurotrophic factors, and overall degeneration of the brain. Adult mesenchymal stem cells (MSCs) offer the potential for a readily available treatment that would be long lasting, have low likelihood of rejection, and could target a variety of pathological deficits. MSCs have been shown to be effective in alleviating symptoms in some transgenic models of AD, but the optimal location for transplanting MSCs has yet to be determined. In the present study, the behavioral effects of transplantation of MSCs into the lateral ventricles, the hippocampus, or both of these regions were compared in the 5xFAD mouse model of AD. The results indicate that MSC transplants effectively reduce learning deficits in the 5xFAD mouse model and demonstrate a clear impact of MSCs on the levels of Aβ42 in the brains of 5xFAD mice. Overall, these findings support the hypothesis that MSCs may be a viable treatment for AD, especially when injected into the lateral ventricles.