Stimulation of nerve growth factor and substance P expression in the iris–trigeminal axis of diabetic rats—involvement of oxidative stress and effects of aldose reductase inhibition

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P<0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P<0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NGF, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes—a mechanism that might participate in iritis.     

Neuropathology in non-human immunodeficiency virus-infected drug addicts: hypoxic brain damage after chronic intravenous drug abuse

Neuropathological studies were carried out on 180 human immunodeficiency virus-seronegative intravenous drug addicts. The findings in victims of acute heroin intoxication (n = 116) were congestion (99.1%), capillary engorgement (68.1%), and/or perivascular bleeding (68.1%) – hemodynamic processes attributable to toxic primary respiratory failure. In a high percentage of these cases (88%), cerebral edema was also present. In 18 cases of acute heroin intoxication who survived for periods of hours or days, the sole postmortem finding was ischemic nerve cell damage, resembling that typically seen in systemic hypoxia. Semiquantitative analysis revealed nerve cell loss in the hippocampal formation and/ or Purkinje cell layer in 26% of the 162 chronic drug abusers. By contrast, in nearly 80% of these cases, the hippocampus showed enhanced expression of glial fibrillary acid protein by astrocytes and/or a proliferation of microglia, demonstrated by CD68 expression. Since such reactive processes are produced by primary neuronal damage, it can be assumed that chronic intravenous drug abuse results in obviously ischemic nerve cell loss. This could be demonstrated in the hippocampus, but it must also occur throughout the whole brain. The demonstration of ischemic nerve cell damage and neuronal loss or secondary reactive alterations has not been described previously. Received: 31 March 1995 / Revised, accepted: 27 November 1995     

NGF prevents the changes induced by monocular deprivation during the critical period in rats

Photic evoked responses were recorded from the striate cortex of Long-Evans hooded intact, monocular visual deprivation (MD) and MD treated with NGF rats. The averaged visual evoked responses (AVER) were obtained from both hemispheres and provided comparison after binocular photic stimuli between the contralateral and the ipsilateral striate cortex with relation to the MD eye. One month of monocular visual deprivation at the critical period of development resulted in marked reduction of the amplitudes of AVER components as compared to the control recordings (P < 0.001). These changes of the AVER could be prevented by NGF infusion to lateral ventricle at the dosage of 2.0–2.4 μg/day for four weeks during the monocular deprivation. In conclusion, the change of AVER amplitudes induced by monocular visual deprivation during the critical period of development can be prevented by NGF infusion to lateral ventricle.     

Local blood flow and metabolism of the tongue before and during panting in the dog

Summary The effects of hyperthermia on blood flow and oxygen consumption of the tongue were investigated in anesthetized dogs. For comparison, blood flow through the skin and deep muscle of the hind leg was also measured in some animals. Increasing blood temperature revealed a biphasic response of lingual blood flow. At 41°C blood temperature respiratory frequency was twice that of control and there was a reduction of lingual blood flow, while resistance of the lingual bed was increased significantly. The arterio-venous oxygen difference (AVDO₂) of lingual blood was markedly increased at this level and the of the tongue was like-wise significantly greater than control. At 41.9°C, the steep increase of respiratory frequency was accompanied by a marked fall in lingual resistance as evidenced by a four-fold increase of lingual blood flow. The systemic AVDO₂ rose at this temperature, while the lingual AVDO₂ fell dramatically. There was no further increase of lingual . At both temperature levels the blood flow through the skin did not change substantially, while the deep muscle blood flow slightly increased. The mean arterial pressure showed a progressive fall during hyperthermia. It is assumed that the decrease of lingual blood flow at elevated blood temperature without panting is due to a redistribution of cardiac output to areas other than the tongue. The increase of lingual blood flow without an additional increase of lingual during panting may be explained solely as a mechanism for heat dissipation. The fact that the decrease of lingual resistance was demonstrated in immobilized animals concomitant with high frequency phrenic burst activity suggests that the decrease of lingual resistance and panting may be induced by a common central integrating mechanism.     

脑内和肌内接种小鼠胶质母细胞瘤株后神经末梢的观察

本实验应用Nonidez及Glees二种镀银法,对诱发的小鼠胶质母细胞瘤株(G 422)进行了观察。脑内及肌内接种胶质母细胞瘤后,在肿瘤边缘可见大小不等的神经束,伴随或不伴随血管伸入瘤内。有的在血管周围间隙形成血管周围神经丛。这些神经纤维与肿瘤周围宿主的脑组织、皮下、毛囊和肌肉间隙的神经纤维相联系。因此我们推测肿瘤内的神经是由肿瘤周围宿主的器官组织的神经延伸来的。肿瘤边缘的神经纤维的数量多于核心区,走行于肿瘤的间质或实质,沿途不断分支,终末分布到肿瘤细胞的表面。我们观察到球形、游离分叉状、梭形、环形、树枝状、杵状及丛刷状等类型的神经末梢。以上观察表明,恶性肿瘤——小鼠胶质母细胞瘤是受神经支配的。     

Recommendations for the examination of peripheral nerve biopsies

 Peripheral nerve biopsy is now an established, valuable investigative procedure, but as it can give rise to significant residual symptoms it should only be undertaken after careful consideration of the indications and with informed consent from the patient. Nerve biopsies should only be processed and evaluated in a laboratory with the relevant particular expertise. It is generally recommended that a sural nerve biopsy be performed in combination with a muscle biopsy but not vice versa (muscle biopsies together with a nerve biopsy). Nerve biopsy is not the only means of sampling peripheral nerve tissue to study the peripheral nervous system. Examination of the innervation of the skin may be informative. The same is likely to be true for motor point muscle biopsy. Nerve biopsy is mainly used for morphology although molecular genetic techniques using fresh or archival nerve biopsies are increasingly available. Chemical analysis is undertaken mainly for research purposes. Received: 10 June 1997 / Accepted: 29 October 1997     

The cerebrospinal fluid transferrin/tau proteins. A study by two-dimensional polyacrylamide gel electrophoresis (2D) and agarose isoelectrofocusing (IEF) followed by double-antibody peroxidase labeling and avidin-biotin amplification

The cerebrospinal fluid (CSF) transferrin/Tau proteins were studied by two-dimensional polyacrylamide gel electrophoresis (2D) followed by immunoblotting and by agarose isoelectrofocusing (IEF), and subsequent double immunofixation, peroxidase staining and Avidin-Biotin Complex (ABC) amplification. The pattern of the Tau protein was similar but not equal to that of the transferrin (Tf). When a genetic variant of Tf was present in the serum, the same variant was also observed in the corresponding CSF Tf and in the Tau fraction. After neuraminidase treatment, both serum and CSF Tf moved to the Tau position on IEF and 2D. On 2D, no desialized precursors of the Tau proteins were detected, whereas the Tf precursors were always detected. No synthesis of the Tau globulin in the brain can, therefore, be inferred. In CSF not treated with neuraminidase, Tf is the only sialoglycoprotein clearly desialized, showing that the Tau fraction cannot be generated by neuraminidase action at CSF level. In fact, the treatment of serum and CSF proteins with neuraminidase produced a clear shift in the isoelectric mobility of all sialoglycoproteins. We clearly demonstrate that the Tau globulin is the result of neuraminidase activity not located in the CSF compartment. We suggest that Tf could be desialized by the action of neuraminidase at the brain level and then be "washed" into the CSF. Brain utilization of Tf, meeting the brain iron requirement, seems likely.