Toll-like Receptor 4 Signaling in Neurons Enhances Calcium-Permeable α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Currents and Drives Post-Traumatic Epileptogenesis.

OBJECTIVE: Traumatic brain injury is a major risk factor for acquired epilepsies, and understanding the mechanisms underlying the early pathophysiology could yield viable therapeutic targets. Growing evidence indicates a role for inflammatory signaling in modifying neuronal excitability and promoting epileptogenesis. Here we examined the effect of innate immune receptor Toll-like receptor 4 (TLR4) on excitability of the hippocampal dentate gyrus and epileptogenesis after brain injury. METHODS: Slice and in vivo electrophysiology and Western blots were conducted in rats subject to fluid percussion brain injury or sham injury. RESULTS: The studies identify that TLR4 signaling in neurons augments dentate granule cell calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (CP-AMPAR) currents after brain injury. Blocking TLR4 signaling in vivo shortly after brain injury reduced dentate network excitability and seizure susceptibility. When blocking of TLR4 signaling after injury was delayed, however, this treatment failed to reduce postinjury seizure susceptibility. Furthermore, TLR4 signal blocking was less efficacious in limiting seizure susceptibility when AMPAR currents, downstream targets of TLR4 signaling, were transiently enhanced. Paradoxically, blocking TLR4 signaling augmented both network excitability and seizure susceptibility in uninjured controls. Despite the differential effect on seizure susceptibility, TLR4 antagonism suppressed cellular inflammatory responses after injury without impacting sham controls. INTERPRETATION: These findings demonstrate that independently of glia, the immune receptor TLR4 directly regulates post-traumatic neuronal excitability. Moreover, the TLR4-dependent early increase in dentate excitability is causally associated with epileptogenesis. Identification and selective targeting of the mechanisms underlying the aberrant TLR4-mediated increase in CP-AMPAR signaling after injury may prevent epileptogenesis after brain trauma. ANN NEUROL 2020;87:497-515.

Patient perception of ideal body weight and the effect of body mass index.

OBJECTIVE: Despite much effort, obesity remains a significant public health problem. One of the main contributing factors is patients' perception of their target ideal body weight. This study aimed to assess this perception. METHODS: The study took place in an urban area, with the majority of participants in the study being Hispanic (65.7%) or African-American (28.0%). Patients presented to an outpatient clinic were surveyed regarding their ideal body weight and their ideal BMI calculated. Subsequently they were classified into different categories based on their actual measured BMI. Their responses for ideal BMI were compared. RESULTS: In 254 surveys, mean measured BMI was 31.71 ± 8.01. Responses to ideal BMI had a range of 18.89-38.15 with a mean of 25.96 ± 3.25. Mean (±SD) ideal BMI for patients with a measured BMI of <18.5, 18.5-24.9, 25-29.9, and ≥30 was 20.14 ± 1.46, 23.11 ± 1.68, 25.69 ± 2.19, and 27.22 ± 3.31, respectively. These differences were highly significant (P < 0.001, ANOVA). CONCLUSIONS: Most patients had an inflated sense of their target ideal body weight. Patients with higher measured BMI had higher target numbers for their ideal BMI. Better education of patients is critical for obesity prevention programs.