GFAP and Fos immunoreactivity in lumbo-sacral spinal cord and medulla oblongata after chronic colonic inflammation in rats

AIM: To investigate the response of astrocytes and neurons in rat lumbo-sacral spinal cord and medulla oblongata induced by chronic colonic inflammation, and the relationship between them. METHODS: Thirty-three male Sprague-Dawley rats were randomly divided into two groups: experimental group (n = 17), colonic inflammation was induced by intra-luminal administration of trinitrobenzenesulfonic acid (TNBS); control group (n = 16), saline was administered intra-luminally. After 3, 7, 14, and 28 d of administration, the lumbo-sacral spinal cord and medulla oblongata were removed and processed for anti-glial fibrillary acidic protein (GFAP), Fos and GFAP/Fos immunohistochemistry. RESULTS: Activated astrocytes positive for GFAP were mainly distributed in the superficial laminae (laminae Ⅰ-Ⅱ) of dorsal horn, intermediolateral nucleus (laminae Ⅴ), posterior commissural nucleus (laminae Ⅹ) and anterolateral nucleus (laminae Ⅸ). Fos-IR (Fos-immunoreactive) neurons were mainly distributed in the deeper laminae of the spinal cord (laminae Ⅲ-Ⅳ, Ⅴ-Ⅵ). In the medulla oblongata, both GFAP-IR astrocytes and Fos-IR neurons were mainly distributed in the medullary visceral zone (MVZ). The density of GFAP in the spinal cord of experimental rats was significantly higher after 3, 7, and 14 d of TNBS administration compared with the controls (50.4±16.8, 29.2±6.5, 24.1±5.6, P<0.05). The density of GFAP in MVZ was significantly higher after 3 d of TNBS administration (34.3±2.5, P<0.05). After 28 d of TNBS administration, the density of GFAP in the spinal cord and MVZ decreased and became comparable to that of the controls (18.0±4.9, 14.6±6.4,P>0.05). CONCLUSION: Astrocytes in spinal cord and medulla oblongata can be activated by colonic inflammation. The activated astrocytes are closely related to Fos-IR neurons. With the recovery of colonic inflammation, the activity of astrocytes in the spinal cord and medulla oblongata is reduced.     

A convenient three dimensional model to teach the arterial supply of the brainstem

An easier approach of teaching the three dimensional nature of arteries of the brainstem is being proposed and aids the understanding of clinical vascular conditions of the brain. Various regions of a standing student appear to represent different parts of the brainstem: head (midbrain), trunk (pons), thigh (medulla oblongata), leg (spinal cord), satchel (cerebellum) and plastic box (fourth ventricle). The vertebral arteries travel proximal to the spinal cord and medulla oblongata and unite at the position of the belt buckle to form the basilar artery. The basilar artery runs superiorly and finally bifurcates laterally at the neck of the student, to form the posterior cerebral artery. The teaching aid is simple, convenient and depicts 19 arteries of brainstem and circle of Willis.     

Tissue-specific expression of the RI and RII sodium channel subtypes.

Anti-peptide antibodies that distinguish between the rat brain sodium channel subtypes referred to as RI and RII were prepared and used to determine their relative expression in nerve and muscle tissues. Sodium channels purified from rat brain are approximately 18% RI and 80% RII. In brain, the RII subtype is preferentially expressed with RI/RII ratios ranging from 0.07 in the hippocampus to 0.17 in the cerebral cortex. The RI subtype is preferentially expressed in more caudal areas of the central nervous system with values of RI/RII of 0.98 for medulla oblongata and 2.2 for spinal cord. Expression of additional unidentified sodium channel subtype(s) is detected in midbrain, medulla, and spinal cord, and expression of unidentified sodium channel subtypes predominates over expression of RI and RII in retina and optic nerve. The RI and RII subtypes are primarily expressed in the central nervous system and are not detected in significant numbers in skeletal or cardiac muscle, sympathetic ganglia, adrenal medulla, sciatic nerve, or cauda equina. The RII subtype appears first in development of both brain and spinal cord but declines in adult spinal cord as the RI subtype increases. The strict regional expression of these two sodium channel subtypes suggests that they may have distinct functional properties or physiological roles.     

Regional brain concentrations of calcitonin gene-related peptide in spontaneously hypertensive and normotensive Wistar-Kyoto rats

The regional brain and spinal cord concentrations of calcitonin gene-related peptide (CGRP) were measured in age-matched (22-23-week-old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The highest concentration of CGRP in the WKY rats was in the spinal cord (172 +/- 9 pmol/g), followed by the medulla oblongata/pons (88 +/- 5 pmol/g). The relative order of distribution in the remaining regions was: hypothalamus (12.6 +/- 0.8 pmol/g) = striatum greater than thalamus greater than midbrain = hippocampus greater than cortex (2.1 +/- 0.3 pmol/g). The concentration of CGRP in the cerebellum was at the level of the assay's sensitivity (0.5 pmol/g). The relative order of distribution in the SHR strain was essentially the same. However, in comparison with the WKY rats, the SHR had significantly lower levels of CGRP in the hippocampus (-47%), striatum (-49%) and medulla oblongata/pons (-24%), and in the spinal cord (-24%). In younger age-matched (16-17-week-old) rats, the spinal cord and medulla oblongata/pons concentrations of CGRP were also lower in SHR than in WKY rats. CGRP is a putative neurotransmitter which, when administered centrally or peripherally, has potent cardiovascular effects. The reduced levels of this peptide may be an important factor in the cardiovascular and/or behavioural abnormalities of the SHR strain.     

Involvement of the Entire Spinal Cord and Medulla Oblongata in Acute Catastrophic-Onset Transverse Myelitis in SLE

A 30-year-old Caucasian male with systemic lupus erythematosus suffered acute catastrophic-onset transverse myelitis. Two years earlier aseptic meningitis, another rare CNS lupus manifestation, had been diagnosed. MRI showed involvement of the medulla oblongata and the entire spinal cord. Therapy with intravenous high-dose methylprednisolone and intravenous cyclophosphamide is discussed. Received: 31 March 1999 / Accepted: 26 September 1999     

A case report of small cell lung cancer with extrahepatic biliary obstruction and intramedullary spinal cord metastasis

A 62-year-old man was admitted to our hospital because of high serum amylase and neck swelling. His chest radiography revealed a mass lesion in the right upper lung. Open lung biopsy specimen established the pathological diagnosis as intermediate type small cell lung cancer. In his clinical course, obstructive jaundice recurred several times with response to combination chemotherapy. The findings of abdominal echogram, computed tomography and endoscopic retrograde cholangiopancreatography suggested that the jaundice was caused by extrahepatic biliary obstruction with parapancreatic lymph node metastasis. He died of spinal bleeding which spread from the medulla oblongata to the thoracic spinal cord. Bleeding was caused by intramedullary spinal cord metastasis. Both extrahepatic biliary obstruction and intramedullary spinal cord metastasis are rare and their symptoms were more prominent than those of the pulmonary lesion.     

Distribution and characterization of immunoreactive corticotropin-releasing factor in human tissues

The distribution and characterization of immunoreactive corticotropin-releasing factor (I-CRF) in human tissues were examined using a rat CRF RIA, immunoaffinity chromatography, gel filtration chromatography, and high performance liquid chromatography. High concentrations of I-CRF were found in the hypothalamus and pituitary stalk. In addition, I-CRF was found in the posterior pituitary, thalamus, cerebral cortex, cerebellum, pons, medulla oblongata, spinal cord, and outside the brain and in the adrenal, lung, liver, stomach, duodenum, and pancreas. The major component of I-CRF from these tissues eluted in the position of rat CRF on gel filtration chromatography. High performance liquid chromatography of this major component showed two main peaks which eluted in the positions of CRF and oxidized CRF. These elution positions were the same in all tissues. These results indicate the presence of I-CRF outside the brain and suggest that this CRF is identical to hypothalamic CRF.     

Distribution of PrP(Sc) in cattle with bovine spongiform encephalopathy slaughtered at abattoirs in Japan

Three 80- to 95-month-old Holstein dairy cattle infected naturally with the agent of bovine spongiform encephalopathy (BSE) and slaughtered at abattoirs in Japan were examined for the distribution of disease-specific and protease-resistant prion protein (PrP(Sc)) by immunohistochemistry (IHC) and Western blot (WB) analyses. The cattle showed no clinical signs or symptoms relevant to BSE but were screened as positive by enzyme-linked immunosorbent assay, a rapid test for BSE. This positive result was confirmed by IHC or WB in a specimen of the medulla oblongata. Histopathologically, these cattle showed no vacuolation in tissue sections from the central nervous system except for the medulla oblongata. Both IHC and WB analyses revealed PrP(Sc) accumulation in the brain, spinal cord, satellite and ganglionic cells of the dorsal root ganglia, and the myenteric plexus of the distal ileum. In addition, small amounts of PrP(Sc) were detected in the peripheral nerves of 2 cattle by WB. No PrP(Sc) was demonstrated by either method in the Peyer's patches of the distal ileum; lymphoid tissues including the palatine tonsils, lymph nodes, and spleen; or other tissues. The distribution of PrP(Sc) accumulation in the preclinical stage was different between naturally infected cattle and cattle inoculated experimentally with the BSE agent.     

Clinical and neuroimaging features of enterovirus71 related acute flaccid paralysis in patients with hand-foot-mouth disease

ObjectiveTo investigate clinical and neuroimaging features of enterovirus71 (EV71) related acute flaccid paralysis in patients with hand-foot-mouth disease.MethodsNine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.ResultsOne extremity flaccid was found in four cases (3 with lower limb, 1 with upper limb), two limbs flaccid in three cases (2 with lower limbs, 1 with upper limbs), and four limbs flaccid in two cases. Spinal MRI studies showed lesion with high signal in T2-weighted images (T2WI) and low signal T1-weighted images (T1WI) in the spinal cord of all nine cases, and the lesions were mainly in bilateral and unilateral anterior horn of cervical spinal cord and spinal cord below thoracic 9 (T9) level. In addition, the midbrain, pons, and medulla, which were involved in 3 cases with brainstem encephalitis, demonstrated abnormal signal. Moreover, spinal cord contrast MRI studies showed mild enhancement in corresponding anterior horn of the involved side, and strong enhancement in its ventral root.ConclusionsEV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior horn regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiently show the characteristic pattern and extent of the lesions which correlated well with the clinical features.     

Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia

The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.     

Time-course changes of nerve growth factor, corticotropin-releasing hormone, and nitric oxide synthase isoforms and their possible role in the development of inflammatory response in experimental allergic encephalomyelitis

In this paper we report a time-course study of development of experimental allergic encephalomyelitis in Lewis rats, by monitoring neuroendocrine regulation of the hypothalamus–pituitary–adrenal axis through corticotropin-releasing hormone mRNA expression, inflammatory cellular infiltrate, macrophagic and neuronal nitric oxide synthase, nerve growth factor (NGF), and NGF p75 and trkA receptors in the brain and spinal cord. We analyzed animals during 20 days after immunization, a time interval that corresponds to the acute immunological phase. We have described a severe, early fall of corticotropin-releasing hormone mRNA expression, which could account for the decreased response of the hypothalamus–pituitary–adrenal axis to inflammatory stress. During this period, an increase of neuronal nitric oxide synthase was observed in the cerebral cortex and spinal cord, and macrophagic nitric oxide synthase positive cells were found in the inflammatory cellular infiltrate, which was abundant in perivascular and submeningeal areas 20 days after immunization. Concomitantly, we found a dramatic up-regulation of NGF receptors on the wall of blood vessels and adjacent neurons in perivascular areas. NGF content also had increased in some brain areas, such as the thalamus, while it had decreased in others, like the spinal cord and medulla oblongata, at time points in which the most serious cellular infiltrate was found.     

国人颈髓角的MRI影像测量及临床意义

目的观察国人颈髓角（CMA）大小,提供其正常值范围,并探讨其临床意义。方法选择301例枕颈区正常的国人MRI片,测量CMA,其中99例同时测量脑干脊髓角。结果 301例受检者的CMA为137.7°～180.0°（163.73°±6.88°）,95%可信区间为150.24°～177.22°,不同性别及不同年龄者的CMA相比,P均〉0.05。其中99例受检者的脑干脊髓角为147.0°～177.7°（162.53°±6.17°）,与CMA相比,P〉0.05。结论国人CMA正常值为137.7°～180.0°,与脑干脊髓角相近,CMA超出正常值范围有助于颅底病变的诊断,对脑干、延髓、颈脊髓压迫程度的评价也有重要参考价值。     

Gastric distention enhances FOS and calcitonin gene‐related peptide expression in the spinal cord and brain of rats

OBJECTIVE: The purpose of this study was to determine the pathway and mode of transmission of visceral stimuli by investigating the distribution of the FOS and calcitonin gene‐related peptide (CGRP) proteins in the central nervous system. METHODS: Twenty‐four Sprague‐Dawley rats were divided into three groups: study group (n = 12), sham control group (n = 6), and normal control group (n = 6). A balloon was implanted into the stomach of the rats in the study and sham control groups. After 48 h, the rats in the study group had the stomach distended (80 mmHg) for 2 h, after which they were killed and the antrum, thoracic spinal cord and brain were isolated or dissected. The expression of Fos and CGRP in these tissues was detected immunohistochemically. RESULTS: FOS expression in the dorsal horn of the spinal cord, dorsal nucleus of the vagal nerve, nucleus of the solitary tract in the study rats was significantly higher than in the sham and normal controls. However, no difference was found between the three groups in FOS expression in the myenteric plexus. Similarly, gastric distention enhanced CGRP expression significantly in the spinal cord and medulla oblongata and correlated closely with FOS expression in these two areas. CONCLUSIONS: Gastric distention can activate the limbic system, and CGRP plays an important role in the input of visceral stimuli.     

Existence of a GnRH immunoreactive nucleus in the dorsal midbrain tegmentum of the chameleon

The GnRH system of the chameleon brain was studied at light microscopic and ultrastructural levels by use of an immunohistochemical technique with antibodies directed against salmon gonadotrophin-releasing hormone. Immunoreactive (IR) perikarya were found in the anterior midbrain tegmentum. At this level numerous IR cell bodies were detected around the fasciculus longitudinalis medialis (FLM). The more rostral neurons were observed dorsal to the FLM and progressively tended to be lateral to it along the midline. More caudally, they were found ventral to the FLM. At the electron microscope level, these cells were seen to contain large granular vesicles and to receive numerous synaptic inputs. A prominent pathway was traced from these cell bodies along the medulla oblongata to the spinal cord. A second IR pathway ascended rostrally to the habenular complex. No IR perikarya were located in the anterior brain including the olfactory bulbs.     

Rectal wall properties in patients with acute and chronic spinal cord lesions

PURPOSE: Most patients with spinal cord injuries suffer from constipation or fecal incontinence. This study was designed to observe rectal wall properties and the rectoanal inhibitory reflex in patients with acute and chronic spinal cord injury. METHODS: Rectal wall properties were studied by rectal impedance planimetry, a method for simultaneous registration of pressure and rectal cross-sectional area during distention. Twenty-five patients with spinal cord injury (14 with supraconal lesions and 11 with conal/cauda equina lesions) were studied one to four weeks after injury, and 17 were available for follow-up after 6 to 14 months. Results were compared with 15 healthy volunteers. RESULTS: Rectal tone was significantly higher (P < 0.05) than normal in patients with acute and chronic supraconal lesions but significantly lower (P < 0.05) in patients with acute and chronic conal/cauda equina lesions. The proportion of subjects with single giant rectal contractions was significantly higher than normal (33 percent) after acute supraconal spinal cord injury (77 percent; P = 0.02) but not after acute conal/cauda equina lesions (45 percent; P = 0.69). Phasic giant contractions only occurred in patients with spinal cord injury (once or more in 8 of 25 patients), but they were not correlated with the level of the lesion. Rectal tone and the number of giant rectal contractions did not change significantly from the acute to the chronic phase of spinal cord injury. The amplitude of the rectoanal inhibitory reflex at distention pressures of 5 and 10 cm H2O was significantly lower than normal in patients with acute and chronic conal/cauda equina lesions (acute, –5 and 44 percent vs. 37 and 82 percent (P < 0.05); chronic, 6 percent (P < 0.05) and 66 percent (P = NS)) but not in patients with supraconal spinal cord injury (acute, 32 and 83 percent; chronic, 61 and 85 percent (all P = NS)). CONCLUSION: Rectal tone is stimulated by the sacral spinal cord but inhibited by supraspinal centers within the central nervous system. Likewise, rectal contractility is inhibited by supraspinal centers, and the rectoanal inhibitory reflex is stimulated by the sacral spinal cord. Alterations caused by either type of spinal cord lesion are present after one to four weeks and do not change significantly within the first year.     

大剂量雌二醇对大鼠血浆和组织中P物质和锌离子含量的影响

采用放射免疫和原子吸收方法．检测雌二醇诱发高血压过程中大鼠血浆和部分组织中P物质和微量元素锌含量的改变。结果表明雌二醇诱发高血压大鼠下丘脑、延脑中P物质含量显著升高．脑垂体、肾上腺和血浆中P物质含量显著降低（P＜0.05～0.01）。延脑、肾上腺和血浆中锌离子升高，肾脏锌离子显著降低（P＜0．05～0．01）。提示P物质参与雌二醇诱发高血压过程；雌二醇可能通过影响心血管中枢、肾上腺、肾脏及血浆中依赖于锌离子的酶的活性而使血压升高。     

多层螺旋CT及三维成像对老年颈椎椎管狭窄的诊断价值

目的探讨三维CT对老年颈椎椎管狭窄的诊断价值。方法对32例行颈部或颈椎检查的病人进行多层螺旋CT横断扫描，扫描后对图像行薄层重建，并传至工作站，应用轴位、多平面成像（MPR）、表面遮盖成像（SSD）、容积成像（VR）及仿真内镜（VE）等方法对有颈椎椎管狭窄的病例图像进行分析。结果32例患者中，18例患者颈椎椎管大小和形态正常，14例病人颈椎椎管均不同程度狭窄，通过不同形式的成像方式可以观察到病变，其中包括骨质增生和椎间盘脱出两种情况，在14例椎管狭窄的病人中，观察到骨质增生38处，颈间盘脱出8处；对于骨质增生的情况，在轴位像上观察到30处，冠状位像上观察到3处，矢状位像上观察到38处，三维图像上观察到21处，仿真内镜像上观察到15处，颈间盘脱出的表现仅能在轴位像上显示。结论多层螺旋CT及三维成像能提供老年性椎管狭窄的精细情况，对颈椎椎管狭窄能立体、直观、全面地展示其原因及程度，为临床治疗提供更充分的信息。     

Brainstem PNMT Neurons and Experimental Hypertension in the Rat

The number of phenylethanolamine-N-methyl transferase (PNMT) cells visualised with immunohistochemical techniques in the medulla oblongata is increased by 20% in 4 week old spontaneously hypertensive rats (SHR) and stroke prone spontaneously hypertensive rats (SHR-SP). This is associated with a 50% increase in the activity of PNMT and a significant rise in the amount of PNMT enzyme protein present in the medulla and spinal cord of both 4 weeks old and 4 months old SHR and SHR-SP.

Since previous experiments had demonstrated that sinoaortic denervation also increased spinal cord PNMT activity we subjected normotensive Wistar Kyoto control rats (WKY) and hypertensive SHR and SHR-SP to denervation and measured the changes in blood pressure and in PNMT activity. Mean arterial pressure rose immediately after denervation in all 3 strains of rats, with much greater rises in the SHR and SHR-SP than in WKY, but the increase in pressure was only sustained in the normotensive WKY, in which it remained elevated throughout the one week observation period. In a similar way, denervation of the arterial baro-receptors increased the activity of PNMT in the medulla and spinal cord of normotensive WKY controls, confirming the results of previous studies but was not able to increase the already elevated PNMT levels in the SHR and SHR-SP any further in these two tissues. We suggest that there is good evidence that PNMT neurons contribute t o the maintenance and elevation of arterial pressure in both the neurogenic and genetic models of hypertension. It also seems likely that the activity of descending spinal PNMT neurons is more important in the maintenance of a sustained increase in pressure than in the induction of a transient rise.     

mRNA for low density lipoprotein receptor in brain and spinal cord of immature and mature rabbits.

Hybridization studies with [32P]cDNA probes revealed detectable amounts of mRNA for the low density lipoprotein (LDL) receptor in the central nervous system (CNS) of rabbits. mRNA levels were highest in the medulla/pons and spinal cord, which were the most heavily myelinated regions that were studied. Lower, but detectable levels were present in cerebral cortex, hypothalamus, thalamus, midbrain, and cerebellum. In the medulla/pons and spinal cord, the levels of receptor mRNA were in a range comparable to that detected in the liver. The levels of receptor mRNA in whole brain were constant from 3 days of age to adulthood and, thus, did not vary in proportion to the rate of myelin synthesis. LDL receptor mRNA in the CNS was produced by the same gene that produced the liver and adrenal mRNA as revealed by the demonstration of a deletion in the neural mRNA of Watanabe-heritable hyperlipidemic (WHHL) rabbits identical to the deletion in the LDL receptor gene of these mutant animals. Using antibodies directed against the bovine LDL receptor, we showed that LDL receptor protein is present in the medulla/pons of adult cows. The cell types that express LDL receptors in the CNS and the functions of these receptors are unknown.