Reactive astrocytes evolve after brain injury, inflammatory and degenerative diseases, whereby they undergo transcriptomic re-programming. In malignant brain tumors, their function and crosstalk to other components of the environment is poorly understood. Here we report a distinct transcriptional phenotype of reactive astrocytes from glioblastoma linked to JAK/STAT pathway activation. Subsequently, we investigate the origin of astrocytic transformation by a microglia loss-of-function model in a human organotypic slice model with injected tumor cells. RNA-seq based gene expression analysis of astrocytes reveals a distinct astrocytic phenotype caused by the coexistence of microglia and astrocytes in the tumor environment, which leads to a large release of anti-inflammatory cytokines such as TGFβ, IL10 and G-CSF. Inhibition of the JAK/STAT pathway shifts the balance of pro- and anti-inflammatory cytokines towards a pro-inflammatory environment. The complex interaction of astrocytes and microglia cells promotes an immunosuppressive environment, suggesting that tumor-associated astrocytes contribute to anti-inflammatory responses.
Preservation of facial nerve and hearing function are not the only important criteria defining QOL after CPA surgery. Tinnitus and vertigo may have a significant underestimated impact on the patient's postoperative course and QOL.
A 56-year-old man was referred to our hospital with complaints of slowly progressive dysesthetic pain in the distribution of the right C-8 nerve root. Symptomatology started approximately eight weeks prior to admission after a two week stay in Africa. Examination on admission revealed motor weakness of the hand intrinsics and abductor pollicis brevis muscle on the right side. Froment's sign was positive and hypesthesia of the fingers 4 and 5 of the right hand was noticed. Deep tendon reflexes were equal and active bilaterally. Neck motion was not limited in any way. The patient did not have any signs of cervical myelopathy. Electromyography which was performed four weeks prior to admission showed pathologic spontaneous activity and signs of axonal degeneration for the right C-8, and to a lesser extent for the right C-7 nerve root. Cervical magnetic resonance (MR) and computed tomogram (CT) images demonstrated spondylosis and osseous narrowing of the right C7/Th1 foramen with compression of the right C-8 nerve root. A CT-guided diagnostic block anesthesia of the right C-8 nerve root with bupivacaine led to temporary total pain relief. Based on clinical findings and diagnostic workup we decided to perform a minimally invasive posterior foraminotomy. Initial postoperative course was uneventful. Significant reduction of preoperative symptoms corresponding to the right C8 nerve root was noted. On the second postoperative day the patient developed new motor deficits on his right arm corresponding to a C-6 and C-7 lesion. Urgently conducted cervical MR imaging failed to show new pathological findings. An extensive blood and CSF workup was initiated in order to rule out bacterial or viral infection. Blood serum and cerebroprinal fluid (CSF) were tested for borreliosis, treponema pallidum, immunglobulines (IgG, IgM, IgA, IgE), Varicella zoster virus (VZV), Herpes simplex virus (HSV) and Human immunodeficiency virus (HIV). The CSF examination revealed 28 leukocytes/mm 3 and an increased protein content of 1920 mg/l. Elevated specific CSF/serum antibody indices for HSV and VZV (3.60 and 2.69 respectively) were verified, indicating an intrathecally production of virusspecific antibodies. Diagnosis of herpes virus-radiculitis was confirmed and intravenous treatment with aciclovir started. Neurological deficits did not, however, resolve during hospital stay but improved considerably after a three month period. DISCUSSION Varicella zoster virus is an alphaherpesvirus causing two distinct syndromes. The primary infection (Chicken pox) usually THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
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