Effects of cortical and thalamic lesions upon primary afferent terminations, distributions of projection neurons, and the cytochrome oxidase pattern in the trigeminal brainstem complex.

Early postnatal lesions of the primary somatosensory cortex alter the vibrissa-related cytochrome oxidase (CO) pattern in nucleus principalis (PrV) of the rat's trigeminal (V) brainstem complex (Erzurumlu and Ebner, '88: Dev. Brain Res. 44:302-308). At present, the reason for this change is not clear. It may be that the corticotrigeminal projection is necessary for the maintenance of vibrissa-related patterns in PrV. However, it is also possible that the loss of the normal pattern of CO activity reflects a change in the organization of brainstem cells resulting from transneuronal retrograde degeneration. In order to address this question, we made lesions of either the primary somatosensory cortex (S-I) or ventrobasal thalamus (VB) in newborn rats and directly assayed distribution of V primary afferents by transganglionic transport of horseradish peroxidase and V-thalamic neurons by retrograde transport of either fluorogold or true blue. Neonatal cortical and thalamic lesions produced no qualitative change in the distribution of primary afferent terminals in either PrV or V subnucleus interpolaris (SpI) beyond that which could be attributed to shrinkage of the brainstem resulting from retrograde degeneration. Most importantly, the "patchy" pattern of terminations observed in normal rats remained apparent in the brain-damaged animals. The normal distribution of V-thalamic neurons in PrV was disrupted by both cortical and thalamic lesions. These cells are normally patterned in a way that matches the distribution of primary afferent terminals and thus that of the mystacial vibrissae. This was not the case in the neonatally brain-damaged rats. Taken together, these results are consistent with the conclusion that neonatal cortical and thalamic lesions disrupt the normal CO pattern in PrV primarily because of their effects upon the patterning of brainstem cells. The present findings demonstrate further that clustering of primary afferents does not require a normal complement of postsynaptic neurons.     

Clinicopathological and genetic correlates of frontotemporal lobar degeneration and corticobasal degeneration

Objective To correlate clinical diagnosis and genetic features with different pathological substrates in patients with frontotemporal lobar degeneration (FTLD) and corticobasal degeneration (CBD). Methods 32 cases with pathological proven FTLD or CBD were selected. Patients were classified clinically as frontotemporal dementia (FTD), progressive nonfluent aphasia (PNFA), semantic dementia (SD), CBD or FLTD with motor neuron disease (FLTDMND). Coding exons 1 and 9–13 of MAPT and exons 0–12 of the PGRN gene were screened by direct sequencing. Regarding the neuropathological findings, cases were classified as tau-positive, ubiquitinpositive tau-negative (FTLD-U), neuronal intermediate filaments inclusions disease (NIFID), dementia lacking distinctive histology (DLDH) or CBD. Results 17 patients were clinically diagnosed with FTD. Ten showed tau pathology, 3 FTLD-U, 1 NIFID and 3 DLDH. All patients clinically classified as FTLD-MND (6 patients) or SD (3 patients) were FTLD-U. Tau-positive pathology was the substrate of the three patients with PNFA. All three patients classified clinically as CBD presented neuropathologic features of CBD. The three individuals with familial history of early onset FTD and tau-positive pathology carried the P301L mutation in the MAPT gene. One out of 3 cases with FTLD-U and intranuclear inclusions carried a mutation in the PGRN gene. Conclusions We found that pathology underlying sporadic FTD is heterogeneous and not predictable. MAPT mutations and clinical diagnosis of PNFA and CBD were associated with tau-positive pathology. The presence of signs of lower MND and SD correlated with FTLD-U.A genetic study of MAPT is only recommended when familial history of early onset DFT is present. * Other members of the Catalan collaborative Study Group for FTLD are listed in the Appendix.     

An unusual association of dentato-rubral degeneration with spinal ataxia,ophthalmoplegia and multiple cranial nerve palsies

Summary Clinical and neuropathological data of a 50-year-old woman with an unusual multisystem degeneration are presented. Clinically the illness was characterized by progressive ataxia with ophthalmoplegia and multiple cranial nerve palsies. Neuropathological investigation showed a severe and selective degeneration of the dentato-rubral system, of the posterior columns and of several cranial nerve nuclei. The problems of differential diagnosis and classification are discussed.     

Deafferentation-induced alterations in the rat dorsal horn: II. Effects of selective poisoning by pronase of the central processes of a peripheral nerve

Studies of deafferentation and regeneration, as well as studies requiring several tracing techniques, would benefit from availability of a substance that would selectively lesion the central components of a single peripheral nerve. Pronase, a combination of proteolytic enzymes, was tested for this purpose. Three weeks following microinjection of Pronase (5-25 mg) into the rat sciatic nerve, many ganglia cells in the L3-L5 ganglia were degenerated. Degeneration of primary afferents also was evident in the dorsal horn, as detected by silver Fink-Heimer methods. Patterns of terminal fields coincided with those mapped in normal rats for the sciatic nerve by using HRP transport. Ultrastructural changes were similar to those seen at 3 weeks following sciatic nerve section or rhizotomy, as described in our companion paper. However, degenerative changes following Pronase injection of the sciatic nerve were quantitatively greater than those following sciatic nerve section alone. Degenerating terminals were either electron lucent and swollen, electron dense, or filamentous with loss of vesicles. Postsynaptic dendrites, and occasionally somata, also showed signs of degeneration. Some became electron dense, others accumulated osmiophilic floccular material, but most became electron lucent and developed large membrane-bound cavities. Glial processes expanded around degenerating elements, wrapping around both terminals and dendrites. Glial sheets covered denervated dendritic and somatic spines, separating them from their terminals. Labyrinth formations of glial sheaths around debris were also found. Pronase appears to mimic the effects of mechanical destruction of primary afferents, but when compared to rhizotomy, is selective for the afferents of a single nerve, and, when compared to nerve section, produces a greater effect. Further, the substance is relatively safe for investigators compared to other toxins such as ricin.     

Focal brain injury and its effects on cerebral mantle, neurons, and fiber tracks

Following a mild cortical impact injury delivered by a piston to the right sensorimotor cortex of the anesthetized rat, we evaluated mantle loss, neuronal changes, and fiber track degeneration by deOlmos silver stains up to 8 weeks after injury. Darkened neurons indicating damage (chromatolysis) occurred widely throughout both hemispheres and were seen from 1 h to 8 weeks after injury. This effect might have occurred from pressure wave damage from piston impact, brain displacement or deafferentation. Cerebral mantle loss was variable but fiber track degeneration related to projection and corticofugal descending tracks associated with the right sensorimotor system was rather constant. Unexpectedly, considerable fiber track degeneration occurred within the cerebellum, especially the inferior vermis. Cells directly under the piston face were surprisingly well-preserved but axon degeneration studies showed that these apparently intact neuronal cell bodies were surrounded by a dense network of degenerating fiber tracks. The intact cells, therefore, may have been functionally cut off from the rest of the brain owing to interruption of their efferents and afferents. The increased susceptibility of axons compared to cell bodies seen with this focal injury is similar to that observed with diffuse brain injury. The early appearing, severe and widespread axon damage we observed suggests that amelioration of focal traumatic brain injury will have to be directed promptly to the preservation of axons as well as cell bodies.     

Tracing of Neuronal Connections in the Human Brain by Magnetic Resonance Imaging in vivo

Axon degeneration after disruption of fibre tracts in the mammalian nervous system is accompanied by myelin breakdown which leads to changes in its magnetic resonance properties. In two patients with pure motor strokes due to small ischaemic lesions restricted to the internal capsule, magnetic resonance imaging disclosed a narrow band of pathological signal increase descending band-like into the brain stem and ascending to the precentral gyrus, which corresponded to the well-known path of the pyramidal tract. The findings suggest that in man anterograde and possibly retrograde fibre degeneration can be traced in vivo by conventional magnetic resonance imaging techniques. Critical conditions are the presence of small, strategically located lesions, appropriate choice of imaging plane, and the interval between time of lesion and of imaging. This demonstration may open a new era for functional neuroanatomy of man.     

腰椎间盘退变的分子病理学变化及发病机制***☆

背景：腰椎间盘退变是引起腰腿痛的常见原因,椎间盘退变的病理改变及发病机制至今仍未完全明确。 目的：介绍腰椎间盘退变的分子病理改变及其发病机制的研究进展。 方法：以“disc histology,disc degenerative disease,disc gene”等主题词检索PubMed数据库,检索时间为2005/2010年,筛选与腰椎间盘组织学变化和发病机制相关的文献,总结归纳腰椎间盘退变的研究进展和研究结果。 结果与结论：共检索到与腰椎间盘退变有关的文章118篇,共纳入30篇。结果表明腰椎间盘退变受多种因素影响,包括基因遗传因素、自然老化和积累性损伤等,基因的多形性是诱发退变的重要前置因素。椎间盘退变可通过免疫反应、机械性压迫或不稳定、血循环障碍和炎性递质等因素导致椎间盘退变性疾病。老化和病理性退变在影像和病理上难以区别,应根据椎间盘退变性疾病的具体情况采取合理的治疗方法,生物学治疗提供了新的治疗思路,但目前仍处在实验研究阶段。     

Characterization of osteopontin expression and function after status epilepticus

Purpose: Osteopontin is a cytokine found in many tissues and plays a role in tissue injury and repair. This study had two goals: to characterize osteopontin expression after status epilepticus (SE), and to test the hypotheses that osteopontin affects the susceptibility to seizures or alters cell death and inflammation after SE. Methods: Pilocarpine was used to induce SE in OPN^?/? and OPN^+/+ mice to compare seizure susceptibility, neuropathological markers including real time PCR for inflammatory genes, and osteopontin immunohistochemistry. The effect of added osteopontin on excitotoxicity by N‐methyl‐d ‐aspartate in neuronal cultures of ONP^?/? mice was determined. Results: Neurons undergoing degeneration showed osteopontin immunoreactivity 2–3  days after SE. After 10 to 31 days degenerating axons in the thalamus were osteopontin‐positive. The susceptibility to seizures of OPN^?/? and OPN^+/+ mice in the pilocarpine, fluorothyl, and maximal electroshock models was similar. There were no significant differences in the extent of neuronal damage after pilocarpine‐induced SE, the expression of several neuropathological markers or the RNA levels of selected inflammatory genes. Recombinant and natural bovine osteopontin did not affect the extent of NMDA‐induced cell death in OPN^?/? mouse neuronal cultures. Conclusion: We demonstrated that osteopontin is up‐regulated in response to SE in distinct temporal sequences in the hippocampus, specifically in dege‐nerating neurons and axons. However, osteopontin did not appear to regulate neurodegeneration or inflammation within the first 3  days after SE.     

Young‐onset multiple system atrophy: Clinical and pathological features

Background: The onset of multiple system atrophy (MSA) before age 40 years is referred to as “young‐onset MSA.” We identified clinical and pathological characteristics that might help with its early diagnosis and distinction from young‐onset Parkinson's disease and late‐onset MSA. Methods: We reviewed the available clinical and pathological features in cases that fulfilled consensus criteria for diagnosis of probable MSA or had autopsy confirmed MSA with an onset before age 40 years and compared the clinical features with 16 autopsy confirmed cases with young‐onset Parkinson's disease and a large published series of late‐onset MSA from the European MSA Study Group. Results: We identified 22 patients with young‐onset MSA, 8 of whom had available pathology. The mean age of onset was 36.7 years (standard deviation 2.3). Levodopa‐induced dyskinesia was more common, whereas myoclonus and pyramidal signs were less common in young‐onset Parkinson's disease when compared with young‐onset MSA. Dystonia, levodopa responsiveness, levodopa‐induced dyskinesia, and pyramidal signs were more common (P < .05) when compared with the data in late‐onset MSA. On postmortem analysis, the minimal‐change pathological variant was more common in young‐onset MSA (n = 2) than late‐onset MSA (P = .045), with a mean survival of 11.1 ± 3.2 years (range 5.5‐14.6) in pathologically confirmed cases of young‐onset MSA. Conclusion: This study has identified useful differences that may improve diagnostic accuracy, help us understand the pathological basis, and assist clinicians with the early diagnosis of young‐onset MSA. © 2018 International Parkinson and Movement Disorder Society     

Myatrophische Lateralsklerose kombiniert mit Degeneration im Thalamus und der Substantia nigra

Summary A 40-year-old man suffering from amyotrophic lateral sclerosis with symmetrical degeneration of the thalamus and the substantia nigra is reported. The distribution pattern of the thalamic degeneration in the present case was characteristic in that the Nucleus centralis was the severest affected of the thalamic nuclei. As far as we know, there is no such case of amyotrophic lateral sclerosis in the literature. Nosologically, this case may represent a form of combined heredosystemic degeneration.

     

Very Slow Retrograde and Wallerian Degeneration in the CNS of C57BL/Ola Mice

Wallerian degeneration following peripheral nerve transection in C57BL/Ola mice is very slow in comparison to other strains of mice. We show that following optic nerve transection, the axons of retinal ganglion cells in C57BL/Ola mice undergo very slow Wallerian degeneration and that retrograde degeneration of the ganglion cell bodies is much slower than in other strains of mice. The results suggest that the gene product affecting Wallerian degeneration in the peripheral nervous system (PNS) also confers a greater resistance to degeneration on central nervous system (CNS) neurons.     

An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters

Summary An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters is reported. A 33-year-old woman showed a progressive dementia and died of cardiac failure at the age of 45. Neurological examination disclosed choreatic movements, myoclonus, rigidity, and generalized convulsion. Gross inspection of the brain showed a diffuse cerebral atrophy and marked degenerations of both the subcortical gray and white matters. Microscopically, numerous and extensive argyrophilic changes such as senile plaques, neurofibrillary tangles, and granulovacuolar degenerations were observed in the brain. The present case was characterized by a severe neuronal loss in the basal ganglia, substantia nigra, dentate nucleus, and thalamus as well as a marked myelin loss and axonal damage in the cerebral white matter. This case suggested a combination of multisystemic degeneration and primary degeneration of the cerebral white matter. The pathological similarity of this case to Creutzfeldt-Jakob disease and Pick's disease is discussed.     

Non-PKC DAG/phorbol-ester receptor(s) inhibit complement receptor-3 and nPKC inhibit scavenger receptor-AI/II-mediated myelin phagocytosis but cPKC, PI3k, and PLCgamma activate myelin phagocytosis by both

Complement-receptor-3 (CR3/MAC-1), scavenger-receptor-AI/II (SRAI/II), and Fcgamma-receptor (FcgammaR) can mediate myelin phagocytosis in macrophages and microglia. Paradoxically, after injury to CNS axons these receptors are expressed but myelin is not phagocytosed, suggesting that phagocytosis is subject to regulation between efficient and inefficient states. In the present work, we focus on CR3/MAC-1 and SRAI/II-mediated myelin phagocytosis. Phagocytosis by CR3/MAC-1 and SRAI/II was inhibited by cPKC inhibitor Go-6976, general-PKC inhibitors Ro-318220 and calphostin-C, and BAPTA/AM, which chelates intracellular Ca2+ required for cPKC activation. Signaling/activation by cPKC are thus suggested. PMA, which mimics diacylglycerol (DAG) as an activator of cPKC, novel-PKC (nPKC), and non-PKC DAG-driven molecule(s), produced a dose-dependent dual effect on phagocytosis by CR3/MAC-1 and SRAI/II, i.e., augmentation at low concentrations and inhibition at high concentrations. Inhibition of phagocytosis by CR3/MAC-1 was enhanced by combining inhibiting concentrations of PMA with PKC inhibitors Go-6976 or Ro-318220, suggesting inhibition by PMA/DAG-driven non-PKC molecule(s). In contrast, inhibition of phagocytosis by SRAI/II was enhanced by combining inhibiting concentrations of PMA with cPKC inhibitor Go-6976 but not with general-PKC inhibitor Ro-318220, suggesting inhibition by nPKC. Phagocytosis by CR3/MAC-1 and SRAI/II was further inhibited by PI3K inhibitors wortmannin and LY-294002 and PLCgamma inhibitor U-73122. Altogether, our observations suggest that CR3/MAC-1 and SRAI/II-mediated myelin phagocytosis share activation by PI3K, PLCgamma and cPKC. The two differ, however, in that non-PKC DAG-driven molecule(s) inhibit CR3/MAC-1-mediated phagocytosis, whereas nPKC inhibit SRAI/II-mediated phagocytosis. Each of these signaling steps may be targeted for regulating CR3/MAC-1 and/or SRAI/II-mediated phagocytosis between efficient and inefficient states.     

Wilson氏病多器官的病理和超微病理学研究

本文对1例HLD死者进行了病理和电镜研究。肉眼可见结节性肝硬化,脾肿大,脑萎缩和豆状核软化灶等。光镜显示坏死后性肝硬化,可见铜离子在肝细胞及其周围沉积;在基底节区可见散在的神经细胞变性,继发性的神经胶质增生,并可找到Alzheimer Ⅱ型细胞。对5种器官(肝、肾、脑、脾和皮肤)进行电镜观察,在肝、肾、皮肤组织均可见散在的高电子密度物质沉积。本研究是国内首次对HLD进行多器官的超微病理学观察,它对促进本病的研究具有重要意义。     

Muscle fiber type morphology and distribution in paraplegic patients with traumatic cord lesion

Summary Previous work showed that lysolecithin injected into rat sciatic nerve produced axonal degeneration of non-myelinated fibres. The possibility was raised that the swollen axons observed proximal to the injection site were the cause rather than the result of axonal degeneration (Mitchell and Caren 1982).The two main objectives of the present study were to examine the effects of different concentrations of lysolecithin on a nerve composed mainly of nonmyelinated fibres and by histochemical means, to study axoplasmic transport in the lysolecithin exposed nerves.The guinea-pig inferior mesenteric ganglion (IMG) and its associated hypogastric nerves, which were ligated, was placed in a three compartment chamber and maintained in vitro for 24 h at 37° C. This in vitro preparation was chosen because the concentration of lysolecithin added to the hypogastric nerves could be accurately measured and axonal transport in the lysolecithin-exposed nerves could be studied using two different methods. Horseradish peroxidase (HRP) applied to the ligated nerve compartment was used to study retrograde transport and the endogenous noradrenaline (NA) content of the sympathetic hypogastric nerves was used to study orthograde transport.The lysolecithin-induced changes were dose dependent and similar to those observed previously in vivo. When the damage was restricted to Schwann cells both HRP and NA were transported along the axons in the lysolecithin-exposed segment of nerve. Only when the lysolecithin produced ultrastructural evidence of axonal degeneration was there any observed accumulation of HRP or NA.These results and the value of this preparation for studying the effects of different toxins on nonmyelinated fibres are discussed.Supported in part by an MRC project grant No. G. 979/622/N     

Degeneration of the cerebellar dentate nucleus in corticobasal degeneration: neuropathological and morphometric investigations

To resolve the controversy regarding the involvement of the dentate nucleus in corticobasal degeneration (CBD), an entire profile of the dentate nucleus was exposed in a sagittal plane and divided into four fields, and the number of neurons in each filed was counted separately using a computer-assisted analyzer in five cases of CBD and compared to those from seven age-matched controls. The size of the nucleus and the number of neurons were significantly reduced in all five cases of CBD. The neuronal loss had a definite regional predilection, more severe in the caudolateral neodentatum than in the rostromedial palaeodentatum, and was accompanied by grumose degeneration and astrogliosis which paralleled the severity of the neuronal loss. Thus, the dentate nucleus appears to be a cardinal target in CBD. Received: 18 May 1999 / Revised, accepted: 27 July 1999     

Ultrastructural Changes of Blood Vessels in the Cerebral Cortex in Alzheimer's Disease

Abstract: Several parts of the cerebral cortices in five brains from patientswith Alzheimer's disease were examined by light and electron microscopes. The results obtained are as follows:
The initial change of the cerebral cortex in the brain occurred in the small blood vessel and capillary. The endothelial cell of the blood vessel fell into a degenerated state with swelling of the vascular feet and astroglial cells. The change in a great number of nerve cells and their processes diffusely observed in the cortices were nonspecific andcould be due to primary vascular degeneration.
Severe dementia in Alzheimer's disease seemed to be well explained by the histo-pathological findings of diffusely destroyed nerve cells and their processes.
From this, Alzheimer's disease can be speculated to be a disease caused by progressive capillary degeneration.     

Reactive glial protein synthesis and early disappearance of saxitoxin binding in degenerating rat optic nerve

Rats implanted with EEG and EMG electrodes were treated with deoxycoformycin (0.5 or 2.0 mg/kg, i.p.), and polygraphically recorded for 6 h. Deoxycoformycin is a potent inhibitor of adenosine deaminase and would be expected to elevate the levels of adenosine in the central nervous system. The 0.5 mg/kg dose of the drug increased REM sleep and reduced REM sleep latency while the dose of 2.0 mg/kg increased deep slow-wave sleep (S2). These results appear to be consistent with those reported previously for the adenosine analog, N6-(L-phenylisopropyl)-adenosine (L-PIA) and indicate a hypnotic role for adenosine.