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Since the first observation that described a patient with a mutation in IL1RAPL1 gene associated with intellectual disability in 1999, the function of IL1RAPL1 has been extensively studied by a number of laboratories. In this review, we summarize all the major data describing the synaptic and neuronal functions of IL1RAPL1 and recapitulate most of the genetic deletion identified in humans and associated to intellectual disability (ID) and autism spectrum disorders (ASD). All the data clearly demonstrate that IL1RAPL1 is a synaptic adhesion molecule localized at the postsynaptic membrane. Mutations in IL1RAPL1 gene cause either the absence of the protein or the production of a dysfunctional protein. More recently it has been demonstrated that IL1RAPL1 regulated dendrite formation and mediates the activity of IL‐1β on dendrite morphology. All these data will possibly contribute to identifying therapies for patients carrying mutations in IL1RAPL1 gene.

Traumatic brain injury (TBI) is one of the leading causes of death and disability in the population worldwide, with a broad spectrum of symptoms and disabilities. Posttraumatic hyperexcitability is one of the most common neurological disorders that affect people after a head injury. A reliable animal model of posttraumatic hyperexcitability induced by TBI which allows one to test effective treatment strategies is yet to be developed. To address these issues, in the present study, we tested human embryonic stem cell–derived neural stem cell (NSC) transplantation in an animal model of posttraumatic hyperexcitability in which the brain injury was produced in one hemisphere of immunodeficient athymic nude rats by controlled cortical impact, and spontaneous seizures were produced by repeated electrical stimulation (kindling) in the contralateral hemisphere. At 14 wk posttransplantation, we report human NSC (hNSC) survival and differentiation into all 3 neural lineages in both sham and injured animals. We observed twice as many surviving hNSCs in the injured versus sham brain, and worse survival on the kindled side in both groups, indicating that kindling/seizures are detrimental to survival or proliferation of hNSCs. We also replicated our previous finding that hNSCs can ameliorate deficits on the novel place recognition task,33 but such improvements are abolished following kindling. We found no significant differences pre- or post-kindling on the elevated plus maze. No significant correlations were observed between hNSC survival and cognitive performance on either task. Together these findings suggest that Shef6-derived hNSCs may be beneficial as a therapy for TBI, but not in animals or patients with posttraumatic hyperexcitability.

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