KATNAL2 mutations have been associated with autism spectrum disorder (ASD) and other related neurodevelopmental disorders (NDDs) such as intellectual disability (ID) in several cohorts. KATNAL2 has been implicated in brain development, as it is required for ciliogenesis in Xenopus and is required for dendritic arborization in mice. However, a causative relationship between the disruption of Katnal2 function and behavioral defects has not been established. Here, we generated a katnal2 null allele in zebrafish using CRISPR/Cas9-mediated genome editing and carried out morphological and behavioral characterizations. We observed that katnal2^-/- embryos displayed delayed embryonic development especially during the convergence and extension (CE) movement. The hatched larvae showed reduced brain size and body length. In the behavioral tests, the katnal2^-/- zebrafish exhibited reduced locomotor activity both in larvae and adults; increased nocturnal waking activity in larvae; and enhanced anxiety-like behavior, impaired social interaction, and reduced social cohesion in adults. These findings indicate an important role for katnal2 in development and behavior, providing an in vivo model to study the mechanisms underlying the ASD related to KATNAL2 mutations.

Scientific efforts continue to concentrate on elucidating the complex molecular mechanisms underlying traumatic brain injury (TBI), and recent reports suggest that epigenetic regulation including long non-coding RNA (lncRNA) is involved. The present study aimed to investigate the plasma concentration of a long non-coding RNA, named growth arrest-specific 5 (GAS5), in a group of 45 patients with severe TBI (sTBI), and to analyze the correlations of GAS5 with TBI onset, injury severity, systemic inflammation, and early outcome of the patients. It was found that plasma GAS5 levels were substantially increased in sTBI patients compared with the relative controls (p < 0.001). Further, significantly higher expression of plasma GAS5 was observed in patients with a Glasgow Coma Scale (GCS) score of less than five (p = 0.002) or unfavorable outcome at discharge (p < 0.001). Circulating GAS5 expression had a negative correlation with GCS score (r = −0.406, p = 0.006), and positive correlations with white blood cell count (r = 0.473, p = 0.001), neutrophil count (r = 0.502, p < 0.001), and neutrophil/lymphocyte ratio (NLR) (r = 0.398, p = 0.007). Univariate and multivariate logistic regression analyses revealed that GCS score (OR = 0.318, 95% CI 0.132–0.767, p = 0.011) and GAS5 (OR = 2.771, 95% CI 1.025–7.494, p = 0.045) were the two independent predictors for early outcome of patients. The receiver operating characteristic (ROC) curves showed good prognostic values of GCS score (AUC = 0.856, 95% CI: 0.719–0.943) and GAS5 expression (AUC = 0.798, 95% CI: 0.651–0.903). Importantly, the combined use of them can improve the prognostic ability of TBI with an AUC of 0.895 (95% CI: 0.767–0.966). Collectively, our study indicated that the levels of lncRNA GAS5 in circulation were elevated following severe TBI and correlated well with injury severity and inflammatory parameters. In addition, GAS5 as well as GCS scores may have the potential to predict the early outcome of TBI patients.

Background: The spontaneous hyperventilation (SHV) accompanying spontaneous cerebellar hemorrhage has yet to attract a sufficient amount of attention. This study aimed to analyze the incidence of SHV in spontaneous cerebellar hemorrhage patients and its risk factors as well as its association with the outcome. Methods: We retrospectively reviewed the medical records of all spontaneous cerebellar hemorrhage patients who underwent surgical treatment at Tongji Hospital from July 2018 to December 2020. Arterial blood gas (ABG) test results and clinical characteristics, including demographics, comorbidities, imaging features, laboratory tests, and therapy choices, were collected. The Glasgow Outcome Scale was used to assess the outcome at two weeks and six months after admission. Results: A total of 147 patients were included, and of these patients 44.9% had spontaneous hyperventilation. Hypertension (OR, 3.175; CI, 1.332–7.569), usage of sedation drugs (OR, 3.693; CI, 1.0563–8.724), and hypernatremia (OR, 2.803; CI, 1.070–7.340) seemed to positively correlate to SHV occurrence. Hematoma removal had an inverse association with SHV (OR, 0.176; CI, 0.068–0.460). Patients with poor and good outcomes had significant differences in pH, PaCO₂, and HCO₃⁻ values, and the severity of SHV was associated with the PaCO₂ level. Conclusions: Spontaneous hyperventilation is common in patients with spontaneous cerebellar hemorrhage, and its severity is associated with the outcome.