Purpose: This study aimed to assess the dynamics of tumor-specific uptake, retention, and blood–tumor barrier penetration of our unique IL-13 receptor α-2 × CD3 bispecific T-cell engager (BTE) following systemic administration in mice with intracranial glioblastoma (GBM) xenografts. Experimental Design: In vitro, BTE binding and accumulation were evaluated in glioma neurospheres. In in vivo studies, the BTEs labeled with either iodine-124 using residualizing chemistry or conjugated to Cy5 were used for longitudinal tracking in patient-derived xenograft models of GBM using PET/CT and confocal microscopy. The survival analysis in mice bearing intracranial GBM tumors was conducted to validate the findings from imaging studies. Results: In vitro, the BTE demonstrated target-specific binding and accumulation in IL-13 receptor α-2–expressing glioma spheres. In vivo, PET/CT imaging revealed that the BTE reached the tumor site within 3 hours after injection, achieving up to 4.8% ID/g, with sustained tumor retention for up to 24 hours, significantly higher than background levels in surrounding normal brain tissue. Confocal microscopy confirmed BTE presence in the tumor bed extravascular space with evidence of T cell–mediated BTE transport across the blood–tumor barrier. Despite its short plasma half-life, the BTE remained in the tumor microenvironment for at least 24 hours. Mice bearing GBM6 brain tumors treated with BTE for 3 to 4 days apart via the intravenous route showed a significant survival advantage over the control group. Conclusions: Our findings provide critical insights into the pharmacokinetics of BTE molecules in GBM. They demonstrate effective penetration and prolonged intratumoral retention following a single systemic dose, supporting further exploration of BTE treatment regimens for translation to clinical settings.

Traumatic Brain Injury (TBI) is a debilitating condition that poses a significant public health concern. Historically linked to motor vehicle accidents, the epidemiology of TBI has evolved. Falls now emerge as the predominant cause, particularly among older adults. Sport-related TBIs have also garnered increased attention due to concerns regarding long-term neurological sequelae. To date, therapeutic interventions remain limited and have yet to yield substantial clinical benefits. Cell-based therapies offer promising avenues for neural repair and regeneration: endogenous stem cell therapies capitalize on endogenous pools that can be triggered by the injury and further enhanced by therapeutic approaches. In contrast, exogenous cell therapies provide an exogenous source of cells. However, challenges such as age-related decline in neurogenesis, age-related inflammation, and the heterogeneity of TBI present significant hurdles to overcome. Moreover, translating stem cell research from the laboratory to clinical applications necessitates the adherence to good manufacturing practice standards, which presents distinct obstacles. Addressing these challenges requires a multifaceted approach, including careful patient selection in clinical trials, appropriate experimental models, and the optimization of therapeutic techniques. Ultimately, a combination of strategies is likely to yield the most promising outcomes in the pursuit of effective TBI therapies.

Subarachnoid hemorrhage (SAH) is a devastating form of stroke that disproportionately affects younger individuals and often results in long-term disability, even among those who achieve favorable outcomes on traditional clinical scales. This scoping review uses the PRISMA-ScR protocol to evaluate independent studies from 1980 to 2025 and synthesizes current evidence on sleep and cognitive dysfunction in SAH survivors, highlighting their prevalence, impact, and gaps in assessment and management. A total of 2243 publications were screened across three databases (PubMed, EMBASE, and Web of Science), which resulted in 115 studies analyzed for review. Sleep disturbances—including insomnia, hypersomnia, and sleep apnea—are common across all phases of recovery and are closely linked to fatigue, mood disorders, and impaired cognitive function. Cognitive deficits, particularly in memory, executive function, and attention, persist in most survivors and are significant barriers to return to work and reintegration. Despite their clinical relevance, these domains are underrepresented in SAH research and inadequately captured by standard outcome measures such as the modified Rankin Scale. Compared to moderate-to-severe traumatic brain injury (TBI), the SAH literature lacks standardized assessment tools, longitudinal data, and interventional studies. Neuroinflammation may underlie both sleep and cognitive sequelae, offering a potential therapeutic target. This review underscores the need for patient-centered outcome measures, integrated sleep and cognitive assessments, and targeted interventions to improve long-term brain health in SAH survivors.

Cerebrospinal fluid (CSF)-directed therapies are gaining importance in neuro-oncology, but long-term CSF access in preclinical murine models remains limited by anatomical constraints. This technical feasibility study evaluates the Transcranial Cisternal Port (TCP), a skull-anchored cannula that provides repeated access to the intrathecal space. The procedure is performed by: making an incision over the craniocervical junction and exposing the cisterna magna; performing a craniostomy on the interparietal bone and placing a guide cannula through it; verifying placement by threading a wire through the cannula and visualizing it within the cisterna magna; securing the cannula in place using surgical adhesive; skin closure and inserting a mandrin to maintain patency. The TCP was validated via Evans blue dye injection, and long-term outcomes were assessed over 3 weeks in 43 athymic nude mice. Evans blue dye distribution was observed throughout the cisterna magna, basal cisterns, and perivascular spaces. All animals recovered uneventfully without device-related complications. Functional retention was 93% at day 7, 86% at day 14, and 86% at day 21. Failure was related to intraluminal clogging (n = 4) and adhesive bonding of the dummy to the guide cannula (n = 2). Revision surgery was successful in all cases. The TCP provides a skull-anchored access route to the murine CSF, enabling reliable intrathecal delivery. Cannula patency remains a limitation in some animals. Future iterations might mitigate this by improving guide cannula design. Overall, these findings establish the TCP as a scalable, functionally robust platform for modeling intrathecal regimens in preclinical studies.