The electrical stimulation model of SE can be used to study mechanisms of SE and its adverse consequences, including death and epileptogenesis.

Objective Generalized convulsive status epilepticus is associated with high mortality. We tested whether α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor plasticity plays a role in sustaining seizures, seizure generalization, and mortality observed during focal onset status epilepticus. We also determined whether modified AMPA receptors generated during status epilepticus could be targeted with a drug. Methods Electrically induced status epilepticus was characterized by electroencephalogram and behavior in GluA1 knockout mice and in transgenic mice with selective knockdown of the GluA1 subunit in hippocampal principal neurons. Excitatory and inhibitory synaptic transmission in CA1 neurons was studied using patch clamp electrophysiology. The dose response of N,N,H,‐trimethyl‐5‐([tricyclo(3.3.1.13,7)dec‐1‐ylmethyl]amino)‐1‐pentanaminiumbromide hydrobromide (IEM‐1460), a calcium‐permeable AMPA receptor antagonist, was determined. Results Global removal of the GluA1 subunit did not affect seizure susceptibility; however, it reduced susceptibility to status epilepticus. GluA1 subunit knockout also reduced mortality, severity, and duration of status epilepticus. Absence of the GluA1 subunit prevented enhancement of glutamatergic synaptic transmission associated with status epilepticus; however, γ‐aminobutyric acidergic synaptic inhibition was compromised. Selective removal of the GluA1 subunit from hippocampal principal neurons also reduced mortality, severity, and duration of status epilepticus. IEM‐1460 rapidly terminated status epilepticus in a dose‐dependent manner. Interpretation AMPA receptor plasticity mediated by the GluA1 subunit plays a critical role in sustaining and amplifying seizure activity and contributes to mortality. Calcium‐permeable AMPA receptors modified during status epilepticus can be inhibited to terminate status epilepticus. ANN NEUROL 2020;87:84–96

Background The purpose of this study is to assess the feasibility of a novel microporous annealed particle (MAP) scaffolding hydrogel to enable both articular cartilage and subchondral bone biointegration and chondrocyte regeneration in a rat knee osteochondral defect model. Methods An injectable, microporous scaffold was engineered and modified to match the mechanical properties of articular cartilage. Two experimental groups were utilized—negative saline control and MAP gel treatment group. Saline and MAP gel were injected into osteochondral defects created in the knees of Sprague-Dawley rats. Photo-annealing of the MAP gel was performed. Qualitative histologic and immunohistochemical analysis was performed of the treated defects at 2, 4, and 8 weeks postsurgery. Results The injectable MAP gel successfully annealed and was sustained within the osteochondral defect at each timepoint. Treatment with MAP gel resulted in maintained size of the osteochondral defect with evidence of tissue ingrowth and increased glycosaminoglycan production, whereas the control defects presented with evidence of disorganized scar tissue. Additionally, there was no significant inflammatory response to the MAP gel noted on histology. Conclusions We have demonstrated the successful delivery of an injectable, flowable MAP gel scaffold into a rat knee osteochondral defect with subsequent annealing and stable integration into the healing wound. The flowable nature of this scaffold allows for minimally invasive application, for example, via an arthroscopic approach for management of wrist arthritis. The MAP gel was noted to fill the osteochondral defect and maintain the defect dimensions and provide a continuous and smooth surface for cartilage regeneration, suggesting its ability to provide a stable scaffold for tissue ingrowth. Future chemical, mechanical, and biological gel modifications may improve objective evidence of cartilage regeneration.

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