differentiation-human-induced-pluripotent-stem-cells-to-brain

Differentiation of Human Induced Pluripotent Stem Cells to Brain Microvascular Endothelial Cell-Like Cells with a Mature Immune Phenotype

Blood-brain barrier (BBB) dysfunction is a pathological hallmark of many neurodegenerative and neuroinflammatory diseases affecting the central nervous ...

Hashimoto's encephalopathy has been described as an autoimmune disorder which demonstrates favorable response to corticosteroid therapy. However, steroid-resistant cases which require additional treatment are frequently reported, and there is no consensus how such cases should be treated. We present a 69 years-old man, who progressed cognitive dysfunction in the past three months. Anti-thyroid and anti-NH terminal of alpha-enolase antibodies were positive. Because initial corticosteroid therapy was ineffective, cyclophosphamide (CPA) pulse therapy was added, and his cognitive function was immediately improved. He had no relapse after tapering dose of corticosteroid for three years. CPA pulse therapy should be considered for steroid-resistant Hashimoto's encephalopathy.

[A case of Hashimoto's encephalopathy successfully treated with cyclophosphamide pulse therapy].

A 60-years-old previously healthy man presented with acute renal failure and hemophagocytic lymphohistiocytosis (HLH). Both conditions improved after immunotherapies, but severe limb weakness with elevation of serum CK developed. Needle EMG showed myogenic changes with spontaneous activities and muscle weakness thereafter improved without adding further immunotherapies, suggesting that our patient had viral myositis. After the stabilization of limb weakness, cecal perforation occurred due to cytomegalovirus (CMV) enteritis and temporal significant change of anti-CMV IgG antibody titer was confirmed using paired serum samples. Upregulation of MHC-class I molecule and numerous regenerative muscle fibers were observed in muscle biopsy, but no evidence of direct CMV infection in muscle fibers were seen. Although CMV infection may cause either myositis, acute renal failure, HLH or colitis in individual patient, this is the first case which had been complicated by all these conditions subsequent to CMV infection.

[Cytomegalovirus myositis complicated with hemophagocytic lymphohistiocytosis, acute renal failure, and colitis].

Isolated adrenocorticotropic hormone deficiency (IAD) is a cause of adrenal insufficiency (AI), which shows impaired secretion of adrenocorticotropic hormone (ACTH) with the preserved secretion of other anterior pituitary gland hormones. We herein report a case of IAD complicated by chronic thyroiditis presenting with neuropsychiatric symptoms without other signs indicative of AI that showed complete improvement of the cognitive function after the administration of corticosteroids. The clinical features of our case may be confused with autoimmune encephalopathies (AEs); however, IAD should be strictly differentiated from AEs, as it requires permanent hormone replacement without addition of immunosuppressive agents.

Cognitive Impairment Caused by Isolated Adrenocorticotropic Hormone Deficiency without Other Hypo-adrenalism Signs - Autoimmune Encephalopathy Mimics.

Many cases of acute flaccid paralysis occurred during an enterovirus D68 (EV-D68) outbreak in North America in the fall of 2014, and this epidemic has been newly defined as a distinct disease entity named acute flaccid myelitis (AFM). This disease entity is relatively popular among pediatricians, whereas it remains little-known among neurologists in Japan. We reported a 7-year-old girl with AFM, in whom severe limb weakness and respiratory failure developed five days after appearance of respiratory symptoms. Clinical features of our case were mimicked by those of acute axonal motor neuropathy at early stage of the disease, and this resulted in delayed diagnosis of AFM. DNA of EV-D68 was not detected. There are few reported cases of severe AFM, in which artificial ventilation is needed for a long time including both acute and recovery phases of the illness, and functional prognosis of AFM is discussed by literature.

[A case of severe acute flaccid myelitis requiring continuous mechanical ventilation].

The Diagnostic process of neurological disorders consists of anatomical and etiological diagnoses, and that of neuropathies usually starts with a suspicion of peripheral nerve disturbance based on neurological findings, which is subsequently confirmed by electrophysiology. However, there are numerous pitfalls in interpreting neurological features and electrophysiological data in the anatomical diagnosis process, possibly leading to misdiagnoses of "neuropathy" in patients with myelopathies, myopathies, neuromuscular junction diseases, or motor neuron diseases. We present the case of a 7-year-old girl showing acute flaccid quadriplegia with overt abnormalities in a nerve conduction study who was initially misdiagnosed with Guillain-Barré syndrome. In retrospect, we recognize several points suggestive of disorders other than neuropathy.

[Peripheral Nerve Disease].

To evaluate the pathophysiology of neuromyelitis optica spectrum disorder (NMOSD) and the therapeutic mechanism and levels of interleukin-6 (IL-6) blockade (satralizumab), especially with respect to blood-brain barrier (BBB) disruption with the new in vitro and ex vivo human BBB models and in vivo model.

New BBB Model Reveals That IL-6 Blockade Suppressed the BBB Disorder, Preventing Onset of NMOSD.

Brain-derived neurotrophic factor (BDNF) cannot cross the blood-brain barrier (BBB) when administered peripherally, which hinders its therapeutic potential. We utilized an in vitro BBB model-a tri-culture of a human endothelial cell line, a pericyte cell line, and an astrocyte cell line-to study the effect of twenty candidate lipophilic compounds on stimulating BDNF secretion in pericytes and astrocytes. The prostaglandin E2 receptor 4 agonist and sphingosine-1-phosphate receptor 5 agonist facilitated secretion of BDNF in the astrocyte, but did not decrease the transendothelial electrical resistance. These compounds may be promising agents for neurodegenerative and neuroinflammatory diseases.

Article	Year
[A case of Hashimoto's encephalopathy successfully treated with cyclophosphamide pulse therapy]. Rinsho shinkeigaku = Clinical neurology\| PubMed ID: 29863104	2018
[Cytomegalovirus myositis complicated with hemophagocytic lymphohistiocytosis, acute renal failure, and colitis]. Rinsho shinkeigaku = Clinical neurology\| PubMed ID: 29962438	2018
Cognitive Impairment Caused by Isolated Adrenocorticotropic Hormone Deficiency without Other Hypo-adrenalism Signs - Autoimmune Encephalopathy Mimics. Internal medicine (Tokyo, Japan)\| PubMed ID: 31366802	2020
[A case of severe acute flaccid myelitis requiring continuous mechanical ventilation]. Rinsho shinkeigaku = Clinical neurology\| PubMed ID: 31474644	2019
[Peripheral Nerve Disease]. Brain and nerve = Shinkei kenkyu no shinpo\| PubMed ID: 32284462	2020
New BBB Model Reveals That IL-6 Blockade Suppressed the BBB Disorder, Preventing Onset of NMOSD. Neurology(R) neuroimmunology & neuroinflammation\| PubMed ID: 34667128	2021
Exploring lipophilic compounds that induce BDNF secretion in astrocytes beyond the BBB using a new multi-cultured human in vitro BBB model. Journal of neuroimmunology\| PubMed ID: 34902709	2022

Kinya Matsuo

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