Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for developing new therapies for TBI. Current treatments for TBI are primarily focused on patient stabilization and symptom mitigation. However, the field lacks defined therapies to prevent cell death, oxidative stress, and inflammatory cascades which lead to chronic pathology. Little can be done to treat the mechanical damage that occurs during the primary insult of a TBI; however, secondary injury mechanisms, such as inflammation, blood-brain barrier (BBB) breakdown, edema formation, excitotoxicity, oxidative stress, and cell death, can be targeted by therapeutic interventions. Elucidating the many mechanisms underlying secondary injury and studying targets of neuroprotective therapeutic agents is critical for developing new treatments. Therefore, we present a review on the molecular events following TBI from inflammation to programmed cell death and discuss current research and the latest therapeutic strategies to help understand TBI-mediated secondary injury.

Trigeminal neuralgia (TN) is a chronic pain condition causing lancinating pain in the distribution of one or more divisions of the trigeminal nerve. Gamma knife stereotactic radiosurgery (GKSRS) is a surgical option for TN refractory to medical therapy. To report our experience and to analyze the reasons for the variance in radiosurgery outcomes between patients in our diverse population, we conducted a retrospective analysis of a prospectively created database. The 178 patients completed a pain assessment questionnaire before surgery, and at 1 and 2 year follow-ups. We used the “Trigeminal Neuralgia Gamma Knife Outcome Scale” (TN GKOS) to report the response. At 1-year, 35.4% of patients had grade 1A outcome (pain-free and off all pain medications), 24.7% had grade 1B (pain-free on pain medications), 24.2% had grade 1C (some pain but improved with radiosurgery), 12.9% had grade 2 (same as before radiosurgery) and 2.8% had grade 3 (worse pain compared to before radiosurgery). At 2 years, 42.3% had grade 1A, 20.5% had grade 1B, 19.2% had grade 1C, 14.1% had grade 2 and 3.8% had grade 3 outcome. Remarkably, a statistically significant association was found between GKOS and age, racial background and obesity.

Alzheimer’s disease (AD) is increasingly recognized as a neurodegenerative disorder characterized by central insulin resistance and cerebral hypometabolism. The steroid hormone, 17β-estradiol (E2), interacts closely with insulin signaling pathways and is locally synthesized in the brain by the enzyme aromatase. However, the spatial and temporal dynamics of brain aromatase during AD progression and its relationship to central insulin resistance remain poorly understood. Using the 5xFAD mouse model, we examined whole-brain, regional, and neuron/astrocyte-specific alterations in aromatase expression along disease progression. Whole-brain aromatase expression remained unchanged at 2 months of age but progressively declined at 5 and 9 months, inversely correlating with amyloid-β plaque burden. Regional analysis of the cortex, hippocampal CA1, and hypothalamus revealed progressive aromatase loss in all regions; notably, the hypothalamus exhibited a significant decline at the earliest disease stage examined, preceding comparable changes in the cortex and hippocampus, while an age-related decline cannot be fully excluded, as only a single-aged wild-type (WT) control was used. Cell-level analysis revealed a progressive reduction in neuronal aromatase expression, whereas astrocytic aromatase displayed a biphasic response, increasing during early disease stages before declining at later stages. In parallel, neuronal insulin-resistance signaling increased progressively with disease advancement and was negatively correlated with neuronal aromatase expression across all regions examined (r = −0.82 to −0.87). Collectively, these findings demonstrate progressive regional and neuron/astrocyte-specific alterations in brain aromatase during the progression of amyloid pathology, identifying early hypothalamic vulnerability as a feature of AD-associated altered insulin signaling.