Intracerebral hemorrhage (ICH) is a devastating form of stroke affecting millions of people worldwide. Parenchymal hematoma triggers a series of reactions leading to primary and secondary brain injuries and permanent neurological deficits. Microglia and macrophages carry out hematoma clearance, thereby facilitating functional recovery after ICH. Here, we elucidate a pivotal role for the interleukin (IL)-4)/signal transducer and activator of transcription 6 (STAT6) axis in promoting long-term recovery in both blood- and collagenase-injection mouse models of ICH, through modulation of microglia/macrophage functions. In both ICH models, STAT6 was activated in microglia/macrophages (i.e., enhanced expression of phospho-STAT6 in Iba1+cells). Intranasal delivery of IL-4 nanoparticles after ICH hastened STAT6 activation and facilitated hematoma resolution. IL-4 treatment improved long-term functional recovery in young and aged male and young female mice. In contrast, STAT6 knockout (KO) mice exhibited worse outcomes than WT mice in both ICH models and were less responsive to IL-4 treatment. The construction of bone marrow chimera mice demonstrated that STAT6 KO in either the CNS or periphery exacerbated ICH outcomes. STAT6 KO impaired the capacity of phagocytes to engulf red blood cells in the ICH brain and in primary cultures. Transcriptional analyses identified lower level of IL-1 receptor-like 1 (ST2) expression in microglia/macrophages of STAT6 KO mice after ICH. ST2 KO diminished the beneficial effects of IL-4 after ICH. Collectively, these data confirm the importance of IL-4/STAT6/ST2 signaling in hematoma resolution and functional recovery after ICH. Intranasal IL-4 treatment warrants further investigation as a clinically feasible therapy for ICH.
Traumatic brain injury (TBI) is exceptionally prevalent in society and often imposes a massive burden on patients’ families and poor prognosis. The evidence reviewed here suggests that gender can influence clinical outcomes of TBI in many aspects, ranges from patients’ mortality and short-term outcome to their long-term outcome, as well as the incidence of cognitive impairment. We mainly focused on the causes and mechanisms underlying the differences between male and female after TBI, from both biological and sociological views. As it turns out that multiple factors contribute to the gender differences after TBI, not merely the perspective of gender and sex hormones. Centered on this, we discussed how female steroid hormones exert neuroprotective effects through the anti-inflammatory and antioxidant mechanism, along with the cognitive impairment and the social integration problems it caused. As to the treatment, both instant and long-term treatment of TBI requires adjustments according to gender. A further study with more focus on this topic is therefore suggested to provide better treatment options for these patients.
Objective: Assess associations between postcochlear implant (CI) auditory training and early outcomes related to speech recognition and CI quality of life (CIQOL). Study Design: Longitudinal, prospective cohort. Setting: Tertiary academic center. Patients: Seventy-two adults undergoing cochlear implantation for bilateral severe-to-profound hearing loss. Interventions: Self-reported use of three categories of auditory training post-CI activation: (1) face-to-face training (e.g., speech pathologist), (2) passive home-based training (e.g., listening to audiobooks), and (3) computer-based training (e.g., interactive software). Main Outcome Measures: Change in Consonant-Nucleus-Consonant phoneme (CNCp), CNC word (CNCw), AzBio sentences in quiet, and CIQOL-35 Profile global and domain scores from pre-CI to 3-month post-CI. Results: Of 72 patients, 52 (72.2%) used an auditory training resource. Of all patients, 18.4% used face-to-face training, 58.3% passive home-based training, and 33.3% computerbased training. At 3 months post-CI, use of any training was associated with greater improvement in speech recognition (d-range ¼ 0.57 -0.85) and global and domain-specific CIQOL scores, except entertainment (d-range ¼ À0.33 to 0.77). Use of computer-based training demonstrated the greatest effect, with larger improvements in speech recognition (CNCp: d ¼ 0.69[0.03,1.35]; CNCw: d ¼ 0.80[0.14,1.46]; AzBio: d ¼ 1.11[0.44,1.77]) and global and all domainspecific CIQOL scores (d-range ¼ 0.05-1.35). Controlling for age, sex, household income, and use of multiple training resources, computer-based training remained the strongest positive predictor of speech recognition and CIQOL improvement, with significant associations with CNCp (ß ¼ 33.07[1,43,64.719]), AzBio (ß ¼ 33.03[5.71,60.35]), and 20.70]) score improvement. Conclusions: Our findings provide preliminary evidencebased recommendations for use of specific auditory training resources for new adult CI recipients. Auditory training, especially self-directed computer software, resulted in improved speech recognition and CIQOL outcomes after 3 months and are widely available for CI users.
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