In rodent models, leukemia inhibitory factor (LIF) is involved in cerebral development via the placenta, and maternal immune activation is linked to psychiatric disorders in the child. However, whether LIF acts directly on neural progenitor cells (NPCs) remains unclear. This study performed DNA microarray analysis and quantitative RT-PCR on the fetal cerebrum after maternal intraperitoneal or fetal intracerebral ventricular injection of LIF at day 14.5 (E14.5) and determined that the expression of insulin-like growth factors (IGF)-1 and -2 was induced by LIF. Physiological IGF-1 and IGF-2 levels in fetal cerebrospinal fluid (CSF) increased from E15.5 to E17.5, following the physiological surge of LIF levels in CSF at E15.5. Immunostaining showed that IGF-1 was expressed in the cerebrum at E15.5 to E19.5 and IGF-2 at E15.5 to E17.5 and that IGF-1 receptor and insulin receptor were co-expressed in NPCs. Further, LIF treatment enhanced cultured NPC proliferation, which was reduced by picropodophyllin, an IGF-1 receptor inhibitor, even under LIF supplementation. Our findings suggest that IGF expression and release from the NPCs of the fetal cerebrum in fetal CSF is induced by LIF, thus supporting the involvement of the LIF–IGF axis in cerebral cortical development in an autocrine/paracrine manner.

Background: A number of childhood diseases have been identified, such as severe infection or autoinflammatory disease, in which immune overreaction against inflammation is a possible underlying mechanism. Previous reports have demonstrated that fetal cells exposed to maternal immune activation (MIA) induced by polyriboinosinic-polyribocytidylic acid [poly(I:C)] exhibited hypersensitivity to inflammation in vitro. However, the details of this mechanism remain unclear. Therefore, this study aimed to reveal the reaction to inflammation in offspring exposed to MIA in the prenatal period, as well as its molecular mechanism, using a viral infection mouse model. Materials and Methods: Pregnant mice at 12.5, 14.5, and 16.5 days post coitum were injected intraperitoneally with poly(I:C) 20 mg/kg body weight (BW) or saline. Offspring aged 3– 4 weeks received the second injection of 20 mg/kg BW or 4 mg/kg BW poly(I:C) or saline. Serum and tissues were collected at 2, 24, 48, and 72 h after the postnatal injection. The cytokine profile, histopathology of organs, and unfolded protein response (UPR) in offspring were examined. Results: The serum levels of interleukin (IL)-6, IL-17, and interferon-γ were significantly higher in the MIA group, and acute liver necrosis was detected. Moreover, failure in UPR was observed in the MIA group compared with that in the control group. Conclusion: Overall, MIA exposure in utero caused failure in UPR as well as immune overreaction to the second attack of inflammation in offspring. Our results suggested that prenatal exposure to MIA might contribute to the congenital inflammatory constitution after birth.

Maternal immune activation has been implicated in the pathophysiology of neurodevelopmental disorders such as autism spectrum disorders caused by maternal infection. It has been suggested that the placental origin of inflammatory cytokines leads to neurodevelopmental disorders. However, the identity of the initial immune-activated site in the placenta, in response to maternal viral infection, is not clear. By cross-breeding male enhanced green fluorescent protein (EGFP) transgenic mice with wild-type females, the placental tissues of maternal origin can be distinguished from those of paternal origin by EGFP expression. Using this method, at embryonic day (E) 12.5, dams were administered an intraperitoneal polyriboinosinic–polyribocytidylic acid (poly [I:C]) injection. We quantitatively analyzed the levels of phosphorylated interferon (IFN) regulatory factor 3 (pIRF3) in the placenta, and investigated the distribution of pIRF3 positive cells. We show that maternally derived decidual cells are the initial target of maternal poly (I:C) through the toll-like receptor 3/TIR-domain-containing the adapter-inducing interferon-β signaling pathway. We also show that the expression of interferon-β was upregulated in the placenta after maternal injection with poly (I:C). These results suggest that maternally derived decidual cells are the initial target of maternal poly (I:C) and that this innate immune response is likely associated with a state of maternal immune activation.

MC5R is known for its role in the exocrine function of sebaceous glands, but other functions in the epidermis remain unclear. This study focused on the relationship between MC5R and homeostasis in the epidermis and examined the role of MC5R in mice whose skin was irradiated with UVB waves. UVB irradiation-induced skin ulcers and severe inflammation at lower doses in homozygotes of MC5R-deficient (i.e., MC5R^−/−) mice (150 mJ/cm²) than the doses in wild-type mice (500 mJ/cm²). Transepidermal water loss was increased (approximately 10-fold) in adult MC5R^−/− mice compared with that in wild-type mice. In neonates, a dye exclusion assay showed no remarkable difference between MC5R^−/− and wild-type mice. After UVB irradiation, compared with wild-type mice, MC5R^−/− mice showed increased inflammatory cell infiltration in the dermis of the ulcerative region, significantly increased thickness of the epidermis in the nonulcerative region, significantly more prickle cells in the nonulcerative region, and increased serum IL-6 levels but decreased IL-10 levels. Transmission electron microscopy revealed fewer lamellar granules, less lipid secretion, and an expansion of the trans-Golgi network in the epidermis in MC5R^−/− mice. This study elucidated the increased sensitivity to UVB irradiation and decreased barrier function in MC5R^−/−mice.

Aphemia is now considered an impairment of speech production. We present a case of an 89-year-old right-handed woman who received intravenous thrombolysis with a recombinant tissue plasminogen activator for the ischemic symptom “loss of speech” and recovered with an ischemic lesion of the left precentral gyrus. The patient had untreated atrial fibrillation. Neurological examination showed that her level of consciousness was alert, with normal comprehension and mild lower facial droop. Head computed tomography (CT) did not reveal a hemorrhagic lesion. To treat the acute ischemic stroke, she received a recombinant tissue plasminogen activator. Just after thrombolysis, she started to speak. Then, magnetic resonance imaging (MRI) revealed an acute ischemic infarction in the dominant precentral gyrus. Follow-up MRI revealed the peripheral middle cerebral artery territory infarction in the left precentral gyrus, but she still could speak. The symptom of “loss of speech” was considered aphemia. By intravenous thrombolysis, impaired speech production in our patient was believed to be caused by an infarction in the dominant precentral gyrus. This case also demonstrated that the rare clinical symptom was due to an ischemic stroke in the territory of the distal middle cerebral artery. Clinicians who engage in stroke care need to know the rare symptoms of aphemia in the era when mechanical thrombectomy could be considered a promising treatment option for distal medium vessel occlusion.

Background: To prevent stroke recurrence, a superficial temporal artery-middle cerebral artery (STA–MCA) bypass for atherosclerotic cerebrovascular occlusive disease is performed. Post stroke epilepsy is known as serious sequelae of stroke. Herein, we present a case of a 60-year-old man who underwent STA–MCA bypass for the prevention of stroke recurrence; however, the donor artery was deemed to be temporally occluded secondary to generalized seizure. Case Description: A 60-year-old man was referred to our hospital with a diagnosis of the left cervical internal carotid artery occlusion presenting with mild aphasia and right hemiparesis. He underwent STA–MCA bypass to prevent the recurrence of stroke 1 month after the onset of symptoms. On postoperative day 7, patency of the donor artery was confirmed on magnetic resonance imaging (MRI), and no complications were noted. However, on postoperative day 14, he presented with a secondary generalized seizure. MRI was immediately performed and the donor artery was not patent with no new lesions. Several hours thereafter, the blood flow of the donor artery was confirmed using pulse Doppler; however, during mouth opening, the flow of the donor artery decreased. Computed tomography-angiography confirmed donor artery patency. An encephalogram was conducted and revealed a focal epilepsy which was compatible with stroke on MRI. Conclusion: Post stroke epilepsy caused an unintended and forced mouth opening which led to a temporary occlusion of the donor artery after STA–MCA bypass. Thus, this complication should be recognized, and seizures should be prevented through the administration of prophylactic anti-seizure medication based on risk stratification assessment of post stroke epilepsy.