Focal brain damage enhances experimental allergic encephalomyelitis in brain and spinal cord

The immunological basis of multiple sclerosis (MS) is well recognized but the factors inducing MS lesions are unclear. In this study, we test the hypothesis that focal brain injury, inflicted during the pre-clinical stages of experimental allergic encephalomyelitis (EAE), will enhance the severity of immunological damage in the cerebral hemispheres and spinal cord. Acute EAE was induced in 30 Lewis rats by the injection of guinea pig spinal cord homogenate in complete Freund's adjuvant. A cryolesion to the surface of the left cerebral hemisphere was induced at 3 days (n=6) or 8 days (n=10) post-inoculation (pi) and animals were killed at 15 days pi. Control animals were EAE only (n = 9), cryolesion only (n=4), EAE and sham cryolesion (n=5) and normal animals (n=3). Brain and spinal cord were stained by immunocytochemistry using W3/13 (T-lymphocytes) OX6 (MHC Class II) and GFAP (astrocytes) antibodies. The results showed a 2-fold increase in the number of EAE lesions in the brain with significant and widespread increase of MHC Class II antigen expression by microglia, in the cryolesion EAE 8 days p.i when compared with EAE only animals. The pattern of enhancement suggests that it is due to (i) local spread of tissue or serum factors from the cryolesion; (ii) neural factors affecting remote regions of the CNS; (iii) stimulation of the immune system which may occur due to products of brain injury draining to regional cervical lymph nodes. Investigation of the mechanisms involved may prove fruitful in establishing factors which initiate, aggravate or ameliorate brain damage in multiple sclerosis.     

Blood-brain and blood-spinal cord barrier permeability during the course of experimental allergic encephalomyelitis in the rat

Experimental allergic encephalomyelitis (EAE) was induced in young male Lewis rats. Blood-brain barrier permeability to radiotracers of different molecular sizes was studied at intervals after induction using a tissue sampling technique. The results were correlated to the clinical picture and to the histological appearance of the central nervous system.Significant increase in blood-brain barrier permeability to small molecules was found to precede clinical symtoms by one day in the lumbar spinal cord and to coincide with the onset of clinical disease in other regions. In all regions, increased blood-brain barrier permeability preceded the occurrence of histological lesions (perivascular cellular infiltrates). No permeability increase to large molecules could be demonstrated.     

Cytokine-induced enhancement of autoimmune inflammation in the brain and spinal cord: implications for multiple sclerosis

Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are autoimmune inflammatory diseases in which cytokines are intimately involved. Here we test the hypothesis that injection of pro-inflammatory cytokines, tumour necrosis factor-alpha (TNFalpha) and interferon gamma (IFNgamma) into the brain of animals in the prodromal phase of EAE significantly enhances inflammation in the central nervous system (CNS). We were particularly interested to learn whether a local increase in cytokines influenced the pathology locally, or more extensively, within the CNS. EAE was induced in female adult Lewis rats. Eight days post-inoculation, TNFalpha or INFgamma was injected into one cerebral hemisphere. Days 11 and 13 post-inoculation (3 and 5 days after the injection of cytokine) inflammation was quantified by the number of perivascular cuffs and the degree of major histocompatibility complex (MHC) class II expression by microglia. Normal animals injected with cytokines, and EAE animals with saline injection served as controls. Results: microglial activation was increased three- to fourfold in the brain and eightfold in the spinal cord (P 相似文献   

Phenotype and function of hematopoietic-derived cells in the CNS of SCID mouse-lewis rat bone marrow chimeras

Severe combined immunodeficient (SCID) mice previously transplanted with Lewis rat hematopoietic cells (SCID mouse-Lewis rat chimeras) developed experimental autoimmune encephalomyelitis (EAE) following injection with myelin basic protein (BP)-specific Lewis rat T lymphocytes. Rat T cells did not cause EAE in non-chimeric SCID mice. Thus, in addition to BP-specific rat T cells, transplanted rat hematopoietic cells were involved in the development of EAE in SCID mice. In order to examine the role of hematopoietic rat cells in the development of EAE, chimeras were constructed in SCID mice by transplanting 40 × 10⁶ T cell-depleted adult Lewis rat bone marrow cells. Single cell suspensions of brain, blood and spleen from chimeric mice were phenotyped by monoclonal antibody staining specific for mouse or rat cellular differentiation markers at 2 week intervals. Brain cells from chimeric mice were also evaluated for the presence of rat antigen-presenting cells (APC). Four and six weeks after hematopoietic cell transfer, mouse brain contained rat cells expressing the phenotypic markers (CD45+, CD11b/c+) of CNS antigen-presenting cells (APC). Six weeks after hematopoietic cell transfer, rat cells populating the CNS of chimeras were shown to function as APC, stimulating BP-specific Lewis rat T lymphocytes in vitro. © 1996 Wiley-Liss, Inc.     

FK506 and a nonimmunosuppressant derivative reduce axonal and myelin damage in experimental autoimmune encephalomyelitis: neuroimmunophilin ligand-mediated neuroprotection in a model of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) in which demyelination and axonal loss result in permanent neurologic disability. We examined the neuroprotective property of the immunosuppressant FK506 (tacrolimus), FK1706 (a nonimmunosuppressant FK506 derivative) and cyclosporin A (CsA) in a chronic relapsing experimental autoimmune encephalomyelitis (EAE) model of MS. Female SJL/J mice were immunized by subcutaneous (s.c.) injection with proteolipid protein 139-151 peptide in complete Freund's adjuvant. At the onset of paralysis, 12-14 days after immunization, mice received daily s.c. injections of FK506 (0.2, 1, and 5 mg/kg), FK1706 (5 mg/kg), CsA (2, 10, and 50 mg/kg), saline or vehicle (30% dimethylsulfoxide) for 30 days. FK506 (at a dose of 5 mg/kg) reduced the severity of the initial disease and suppressed relapses. FK1706 did not significantly alter the clinical course and CsA (at a dose of 50 mg/kg) lessened the severity of the initial episode of EAE but did not alter relapses. In the thoracic spinal cord, FK506 (5 mg/kg), FK1706 (5 mg/kg), and CsA (50 mg/kg) significantly (P < 0.001) reduced the extent of damage in the dorsal, lateral, and ventral white matter by a mean of up to 95, 68, and 30%, respectively. A nonimmunosuppressant dose of FK506 (0.2 mg/kg) also significantly (P < 0.001) reduced the extent of damage in the spinal cord by a mean of up to 45%. Other dosages of these compounds were ineffective. FK506 markedly protects against demyelination and axonal loss in this MS model through immunosuppression and neuroprotection.     

Acute Akinesia,an unusual complication in Parkinson’s Disease: a case report

Acute akinesia (AA) is a rare but serious complication of Parkinson's Disease (PD) 0,3% of all patients with PD). It can be related to infectious condition, surgery, or treatment changes. AA can completely recover or result in some motor deficits, and, in the most severe forms, it may lead to untreatable complications and death. Here we report the case of a 67-year-old man with PD who rapidly developed a severe akinetic state with rise of temperature (39 degrees C) and creatine phosphokinase concentration (up to 5000 mg/dL). After excluding infection diseases and other pathologies, we suspected AA and added apomorphine 50mg/die s.c. and ondansetron 8 mg i.v. The patient responded to treatment and ameliorated in few weeks.     

Neuroimaging and neurologic findings in COVID-19 and other coronavirus infections: A systematic review in 116 patients

Various neurologic syndromes have been described in patients with COVID-19 and other coronavirus infections. In this paper, we systematically reviewed the available imaging findings of patients diagnosed with neurological symptoms associated with coronavirus infections. Diverse radiologic results in the context of different neurologic presentations have been demonstrated using CT and MRI. While many patients have normal imaging evaluations, some patients present with intra-axial and extra-axial abnormalities. Stroke (both ischemic and hemorrhagic), encephalomyelitis, meningitis, demyelinating disorders such as acute disseminated encephalomyelitis (ADEM), and encephalopathy have been reported. Familiarity with these radiologic patterns will guide radiologists and referring clinicians to consider coronavirus infections in patients with worsening or progressive neurologic findings, particularly during the current COVID-19 pandemic. As data on this topic is very limited, further research and investigation are required.     

The relationship of current depressive symptoms and past depression with cognitive impairment and instrumental activities of daily living in an elderly population: the Sydney Memory and Ageing Study

Depressive symptoms are common in the elderly and they have been associated with cognitive and functional impairment. However, relatively less is known about the relationship of a lifetime history of depression to cognitive impairment and functional status. The aim of this cross-sectional study was to assess whether current depressive symptoms and past depression are associated with cognitive or functional impairment in a community-based sample representative of east Sydney, Australia. We also examined whether there was an interaction between current and past depression in their effects on cognitive performance. Eight hundred non-demented aged participants received a neuropsychological assessment, a past psychiatric history interview and the 15-item Geriatric Depression Scale. The Bayer-Activities of Daily Living scale was completed by an informant to determine functional ability. Clinically relevant depressive symptoms were present in 6.1% of the sample and 16.6% reported a history of depression. Participants with current depression had significantly higher levels of psychological distress and anxiety, and lower life satisfaction and performed worse on memory and executive function compared to participants without current depression. After controlling for anxiety the effect on executive function was no longer significant while the effect on memory remained significant. A history of depression was associated with worse executive function, higher levels of psychological distress and anxiety, and lower life satisfaction. After controlling for psychological distress the effect of past depression on executive function was no longer significant. There were no significant interactions between current and past depression in their effects on cognitive performance. There were no differences between participants with or without current depression and with or without past depression on functional abilities. These results support the view that current and past depressive episodes are associated with poorer cognitive performance but not with functional abilities.     

Decreased levels of PSD95 and two associated proteins and increased levels of BCl2 and caspase 3 in hippocampus from subjects with amnestic mild cognitive impairment: Insights into their potential roles for loss of synapses and memory,accumulation of Aβ, and neurodegeneration in a prodromal stage of Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia and is pathologically characterized by senile plaques, neurofibrillary tangles, synaptic disruption and loss, and progressive neuronal deficits. The exact mechanism(s) of AD pathogenesis largely remain unknown. With advances in technology diagnosis of a pre‐AD stage referred to as amnestic mild cognitive impairment (MCI) has become possible. Amnestic MCI is characterized clinically by memory deficit, but normal activities of daily living and no dementia. In the present study, compared to controls, we observed in hippocampus from subjects with MCI a significantly decreased level of PSD95, a key synaptic protein, and also decreased levels of two proteins associated with PSD95, the N‐methyl‐D‐aspartate receptor, subunit 2A (NR2A) and the low‐density lipoprotein receptor‐1 (LRP1). PSD95 and NR2A are involved in long‐term potentiation, a key component of memory formation, and LRP1 is involved in efflux of amyloid beta‐peptide (1‐42). Aβ (1‐42) conceivably is critical to the pathogenesis of MCI and AD, including the oxidative stress under which brain in both conditions exist. The data obtained from the current study suggest a possible involvement of these proteins in synaptic alterations, apoptosis and consequent decrements in learning and memory associated with the progression of MCI to AD. © 2009 Wiley‐Liss, Inc.