Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

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Astrocytes: biology and pathology

Pathobiology of ischaemic stroke: an integrated view

This review is directed at understanding how neuronal death occurs in two distinct insults, global ischemia and focal ischemia. These are the two principal rodent models for human disease. Cell dea...

Ischemic Cell Death in Brain Neurons

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy.

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IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel.

Over the past two decades, research has heavily emphasized basic mechanisms that irreversibly damage brain cells after stroke. Much attention has focused on what makes neurons die easily and what strategies render neurons resistant to ischaemic injury. In the past few years, clinical experience with clot-lysing drugs has confirmed expectations that early reperfusion improves clinical outcome. With recent research emphasizing ways to reduce tissue damage by both vascular and cell-based mechanisms, the spotlight is now shifting towards the study of how blood vessels and brain cells communicate with each other. This new research focus addresses an important need in stroke research, and provides challenges and opportunities that can be used to therapeutic advantage.

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Mechanisms, challenges and opportunities in stroke

Moyamoya syndrome (MMS) is an uncommon late complication after cranial irradiation. Its hemorrhagic presentation from the associated pseudo-aneurysm is extremely rare, and the optimal management strategy is undetermined. We herein report a 36-year-old man who developed intraventricular hemorrhage from a pseudo-aneurysm at the extended left anterior choroidal artery as an abnormal collateral of MMS 30 years after surgical removal and cranial irradiation for childhood craniopharyngioma. Catheter angiography confirmed the diagnosis of MMS, and multiple pseudo-aneurysms were evident at the ipsilateral abnormal choroidal collateral, one of which was considered to be a source of bleeding. The patient underwent left superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis with indirect pial synangiosis based on the observation that the development of choroidal collateral may be associated with a high rebleeding risk in hemorrhagic moyamoya disease. The patient was discharged without neurological deficit, and postoperative magnetic resonance angiography confirmed the STA-MCA bypass to be patent. Catheter angiography 1 year after revascularization surgery revealed the complete disappearance of the pseudoaneurysms with the apparently patent STA-MCA bypass. The patient did not exhibit any cerebrovascular events during the follow-up period of 16 months. In conclusion, hemorrhagic MMS with choroidal collateral as a dangerous anastomosis was effectively managed by STA-MCA anastomosis. Although long-term follow-up is necessary to evaluate our strategy, the favorable disappearance of pseudoaneurysms after revascularization surgery in the present case strongly suggests that STA-MCA anastomosis has a potential role for preventing rebleeding in MMS after cranial irradiation.

Efficacy of Direct Revascularization Surgery for Hemorrhagic Moyamoya Syndrome As a Late Complication of Cranial Irradiation for Childhood Craniopharyngioma.

Among brainstem arteriovenous malformations (AVMs), there exist small AVMs predominantly located in the cerebellopontine angle cistern (CPAC) with minimal extension into the pial surface of the brainstem. However, previous studies of CPAC AVMs did not particularly discuss the role of embolization in the treatment of these lesions. This study was conducted to clarify the effectiveness and validity of embolization in the treatment of CPAC AVMs. We retrospectively reviewed five patients with CPAC AVMs who underwent endovascular treatment. These patients were treated with embolization followed by open surgery or gamma knife (GK) radiosurgery. Radiological findings and clinical course for these patients were then assessed. All five patients presented with a hemorrhage. Angiography revealed that the main feeder contained a dilated pontine perforating artery in all cases. Embolization through the dilated pontine perforating artery effectively reduced shunt flow within the nidus or obliterated associated aneurysms. Magnetic resonance imaging showed infarction on the lateral pons in four patients, one of which developed transient mild dizziness and mild ataxia of the right side. Subsequent open surgery was performed in three patients, and GK radiosurgery was performed in two patients without complications. At the end of the follow-up period, all patients demonstrated favorable outcomes. Postoperative rebleeding did not occur in any of the patients. Disappearance of the AVM was confirmed in four patients, except in the one patient treated with GK. Although ischemic complications should be noted, embolization of CPAC AVMs may be an appropriate treatment option to reduce the risk of subsequent surgery or radiosurgery.

Embolization of ruptured arteriovenous malformations in the cerebellopontine angle cistern

Most cases of optic hypothalamic pilocytic astrocytoma (OHPA) develop during childhood, so few cases of histologically verified OHPA have been described in adolescents and young adults (AYA). To elucidate the clinical features of OHPA with histological verification in AYA, we reviewed the clinical and radiological finding of OHPA treated at our institute from January 1997 and July 2017. AYA are aged between 15 and 39 years. The clinical courses of 11 AYA patients with optic hypothalamic glioma (OHG) without neurofibromatosis type 1 were retrospectively reviewed. About six patients were diagnosed in childhood and followed up after 15 years of age, and five patients developed OHPA during AYA. Histological diagnosis, verified at initial presentation or recurrence, was pilocytic astrocytoma in 10 and pilomyxoid astrocytoma in one. After initial treatment including debulking surgery and/or chemotherapy, tumor progression occurred 16 times in seven patients as cyst formation, tumor growth, and intratumoral hemorrhage. Five of 10 patients suffered deterioration of visual function during AYA. One of 10 cases had endocrinopathies requiring hormone replacement at last follow-up examination. In conclusion, histological diagnoses of OHG before and in AYA were pilocytic astrocytoma or pilomyxoid astrocytoma. Both pediatric and AYA-onset OHPA demonstrate high incidences of tumor progression and visual dysfunctions in AYA, so that long-term follow up is essential after the completion of treatment for pediatric and AYA-onset OHPA. The optimal timing of debulking surgery and radiation therapy should be established to achieve the long-term tumor control and to preserve the visual function.

Frequent Clinical and Radiological Progression of Optic Pathway/Hypothalamic Pilocytic Astrocytoma in Adolescents and Young Adults

A contralateral extra-axial hematoma sometimes occurs during an operation on an acute subdural hematoma and may become fatal. Using a combined procedure of burr hole evacuation and craniotomy, we treated 2 cases of multiple traumatic acute subdural hematomas. Our policy for such cases is first to perform a burr hole evacuation for the acute subdural hematoma in the emergency room, while simultaneously preparing the operation room for a possible further operation. Next, we perform computed tomography (CT) of the brain. If the evacuation does not provide enough decompression, we either carry out a craniotomy at the same site, or, we observe the patient without resorting to craniotomy. However, if the patient's condition deteriorates, burr hole evacuation is repeated and/or craniotomy is carried out as soon as possible on the lesion at the already prepared operation room. Both of our patients received craniotomy for another subdural hematoma after the burr hole evacuation. Though his intracranial pressure was well managed during the acute stage, one of the patients died 21 days after the trauma due to an extensive brain infarction caused by vasospasm. The other regained consciousness and was able to walk 5 months after the trauma in spite of cerebral infarction from vasospasm. The possible mechanism of vasospasm in severe head injury is also discussed.

[Two cases of impending herniation due to multiple traumatic acute subdural hematomas: combination of burr hole evacuation and craniotomy].

Blue naevus is a congenital benign melanocytic lesion originating from a disorder of the neural crest. Blue naevus generally occurs in the skin, and can affect the eyelids and surrounding tissue. There are two types of blue naevus, common blue naevus and the cellular blue naevus (CBN). Unlike the common blue naevus, CBN can, in rare instances, undergo transformation into malignant melanoma. But contiguous intracranial invasion by CBN is extremely rare [1, 3–5].

Miki Fujimura

Papers

Efficacy of Direct Revascularization Surgery for Hemorrhagic Moyamoya Syndrome As a Late Complication of Cranial Irradiation for Childhood Craniopharyngioma.

Embolization of ruptured arteriovenous malformations in the cerebellopontine angle cistern

Frequent Clinical and Radiological Progression of Optic Pathway/Hypothalamic Pilocytic Astrocytoma in Adolescents and Young Adults

[Two cases of impending herniation due to multiple traumatic acute subdural hematomas: combination of burr hole evacuation and craniotomy].

A case of cellular blue naevus with intracranial invasion and malignant transformation.