天麻素对单侧前庭功能丧失大鼠绒球中谷氨酸免疫反应物、胶质纤维酸性蛋白、γ-氨基丁酸B2型受体表达及疗效的影响

目的　探讨天麻素促进前庭功能恢复及中枢代偿的机制。方法　成年健康SD大鼠随机分组,空白对照组（n=9）正常饲养,假手术对照组（n=18）鼓室内注射生理盐水,模型对照组（n=18）、模型治疗组（n=54）鼓室内注射氯仿。造模成功后,对照组肌肉注射生理盐水;模型治疗组再随机分为天麻素低、中、高剂量组（每组n=18）,每日分别肌肉注射低、中、高剂量天麻素,连续注射3d。观察绒球中谷氨酸免疫反应物（glutamate immunoreactivity,GLU-IR）、胶质纤维酸性蛋白（giial fibrillary acid protein,GFAP）、γ-氨基丁酸B2型受体（gamma-aminobutyric acid B2,GABA B2）表达。结果　模型对照组、模型治疗组GLU-IR表达明显下调,GFAP、GABA B2表达明显上调。经天麻素治疗后,模型治疗组与模型对照组比较,GLU-IR、GABAB2表达明显上调,GFAP表达明显下调,天麻素高剂量组均最为明显。结论　天麻素能够对中枢进行多靶点调控,加速代偿的进程与程度。     

Afferent projection from the dorsal nucleus of the raphe to the flocculus in cats

Horseradish peroxidase (HRP) was injected iontophoretically into the cerebellar flocculus in cats. The neurons labeled with HRP were recognized in the caudal part of the dorsal nucleus of the raphe. Electrical stimulation of this region elicited orthodromic evoked potentials in the flocculus and stimulated sites of low threshold current necessary to evoke the responses were limited in a small area corresponding well with the dorsal nucleus of the raphe.     

Electrophysiological study of the nucleus of the optic tract that transfers optic signals to the nucleus reticularis tegmenti pontis—the visual mossy fiber pathway to the cerebellar flocculus

Neuronal activities (n = 43) in the pretectal region in rabbits were recorded. They were orthodromically activated from the optic chiasm (latency, 1.86 ± 0.35msec) and antidromically from the ipsilateral nucleus reticularis tegmenti pontis (Nrt) (latency, 0.97 ± 0.22sec). Thirty-one (72%) neurons were in the nucleus of the optic tract (NOT), four (9%) in the anterior pretectal nucleus (PA) and seven (16%) in the border between NOT and PA. These findings demonstrate that the NOT is involved in the visual mossy fiber pathways to the flocculus and may contribute to optokinetic eye movements.     

Vestibular afferents of the inferior olive and the vestibulo-olivo-cerebellar climbing fiber pathway to the flocculus in the cat

The projection of the vestibular nuclei to the inferior olive was investigated by means of anterograde transport of tritiated leucine. Following injections in the medial and descending vestibular nuclei, terminal labeling was found ipsilaterally in the dorsomedial cell column, subnucleus beta and the caudal medial accessory olive, while the latter also received afferents from the nucleus prepositus hypoglossi. At the contralateral side termination in the dorsomedial cell column and the medial accessory olive was found after injections in the nucleus vestibularis superior and group Y. The ventrolateral outgrowth and different parts of the principal olive also received afferents from these two nuclei and also from ventral parts of the lateral cerebellar nucleus. The dorsal cap was labeled exclusively from the contralateral nucleus prepositus hypoglossi. The termination in the inferior olive of the vestibular afferents is compared with the projection from a number of pretectal nuclei. Furthermore the consequences of the divergence and convergence of both types of projections at the level of the inferior olive is discussed in relation to the subsequent climbing fiber projection to the flocculus.     

Floccular influence on excitatory relay neurones of vestibular reflexes of anterior semicircular canal origin in the cat

Floccular influence on excitatory vestibular reflex arcs of anterior semicircular canal origin was examined in the anaesthetized cat. Stimulation of the anterior semicircular canal nerve (ACN) evoked disynaptic excitatory postsynaptic potentials (EPSPs) in all sampled inferior oblique (IO), superior rectus (SR), and biventor cervicis (BIV) muscle motoneurones of the contralateral side. Conditioning stimulus to the flocculus depressed the amplitude of the EPSPs in both IO and SR motoneurones by 50% on the average but not in any BIV motoneurones. The excitatory vestibulo-ocular neurones identified by orthodromic and antidromic responses to stimulation of the ACN and the contralateral IO motoneurone pool, respectively, were classified as VOC (vestibulo-ocular neurones with axons descending to the cervical segment) or VO (vestibulo-ocular proper) neurones on the basis of whether or not they responded antidromically to stimulation of the spinal cord in the C1 segment. All of the VO neurones in the superior vestibular nucleus (n = 19) were inhibited from the flocculus while the activities of three-fourths of the VO neurones (36/48) in the other vestibular nuclei were not suppressed by floccular stimulation. In contrast, none of VOC neurones (n = 49) received floccular inhibition. Besides inhibition, floccular stimulation induced the antidromic or orthodromic responses in some VO and VOC neurones.     

Afferent projections from the brainstem to the three floccular zones in cats. I. Climbing fiber projections

The cat's flocculus can be divided into 3 zones on the basis of differences in their efferent projection sites. In the present study, climbing fiber projections from the inferior olive to each zone of the flocculus were studied by means of retrograde axonal transport of horseradish peroxidase (HRP). Following large injections of HRP into the flocculus, labeled cells appear in the dorsal cap and the ventrolateral outgrowth of the principal olive. No HRP-labeled somata are present in other parts of the inferior olive. Following microinjections of HRP into the rostral of caudal zones of the flocculus, labeled cells appear in the ventrolateral outgrowth and the rostral part of the dorsal cap, while, after injections into the middle zone, labeled cells are found in the caudal part of the dorsal cap. These findings show that there exists zonal organization in the climbing fiber projections to the flocculus; the rostral and caudal zones receive climbing fiber afferents from the ventrolateral outgrowth and the rostral part of the dorsal cap, while the middle zone receives those from the caudal part of the dorsal cap.     

Effects of electrical stimulation and reversible lesions of the olivocerebellar pathway on Purkinje cell activity in the flocculus of the cat

The activity of Purkinje cells (P-cells) in the flocculus of 8 lightly anesthetized cats and one alert cat was recorded for periods of up to several hours each. The resting simple spike (SS) rate in the anesthetized cats was 37 +/- 21 Hz (mean +/- standard deviation), similar to that observed in the alert cat. Complex spikes (CSs) were evoked by an electrode placed in the climbing fiber (CF) decussation or inferior olive (IO). For each P-cell, SS activity was suppressed completely at or above a cut-off frequency of evoked CSs; median cut-off rate was 5 Hz (range 1-10 Hz, 15 cells). Reversible lesions of the CF pathway were made by microinjection of 1-10 microliter of saturated lidocaine into the IO or CF decussation. This abolished spontaneous CS activity and produced two reversible effects on SS discharge: (1) an increase in mean SS rate of 98%, from 23 +/- 13 to 40 +/- 18 Hz (11 cells); and (2) a decrease of 50% in the variability of SS firing rate. Similar effects were observed in two P-cells whose CF axons were lesioned mechanically. These results show that electrical stimulation and reversible lesions in areas previously shown to alter the gain of the vestibulo-ocular reflex (VOR) also alter CF input to the flocculus, suggesting that the gain changes were caused by changes in CS rate. This study confirms and extends the observation that a reciprocal relationship exists between CS rate and SS background rate, and therefore further suggests that the changes in the gain of the VOR might be due to changes in SS background rate.     

Reorganization of longitudinal compartments in the laterally protruding paraflocculus of the postnatal mouse cerebellum

The paraflocculus and the neighboring smaller flocculus form a remarkable protrusion in the ventrolateral aspect of the mouse cerebellum, in which the longitudinal compartments are conspicuously oriented perpendicularly to the sagittal plane. The developmental process of such anatomical arrangements in these lobules has not been fully clarified. Here, we used the genetic tractability of pcdh10-lacZ knock-in (OL-KO), IP ₃R1-nls-lacZ transgenic (1NM13) and Gpr26cre-Ai9-AldocV mice to track the development of compartments and examined local longitudinal orientation of Purkinje cells within the paraflocculus and flocculus. We observed a distinct pcdh10-positive (pcdh10+) compartment in the flocculus, whereas the paraflocculus and other lobules had a continuous paravermal pcdh10+ compartment, in the embryonic OL-KO cerebellum. During the first postnatal week, the parafloccular pcdh10+ compartment shifted laterally to the most lateral edge in the caudal part of the protruding paraflocculus. Although the most medial edge of the parafloccular pcdh10+ compartment remained in the nonprotruding part of the paraflocculus, it was disrupted from the originally continuous pcdh10+ compartment in the copula pyramidis. The local longitudinal orientation changed gradually along with the mediolateral extent of the copula pyramidis, almost becoming perpendicular to the sagittal plane in the laterally connected paraflocculus in the adult cerebellum. This rotational change in orientation was derived from the short U-shaped embryonic cerebellum, in which the surfaces of the flocculus and paraflocculus were oriented laterally. These results indicated that the peculiar compartmental organization of the paraflocculus originates from the embryonic common hemispheric compartmental organization and shaped by the significant reorganization process in the first postnatal week.     

Bilaterally Abnormal Head Impulse Tests Indicate a Large Cerebellopontine Angle Tumor

MethodsTwenty-eight patients (21 women; age=64±12 years, mean±SD) with a unilateral CPA tumor underwent a recording of the HITs using a magnetic search coil technique. Patients were classified into non-compressing (T1-T3) and compressing (T4) groups according to the Hannover classification.ResultsMost (23/28, 82%) of the patients showed abnormal HITs for the semicircular canals on the lesion side. The bilateral abnormality in HITs was more common in the compressing group than the non-compressing group (80% vs. 8%, Pearson''s chi-square test: p<0.001). The tumor size was inversely correlated with the head impulse gain of the VOR in either direction.ConclusionsBilaterally abnormal HITs indicate that a patient has a large unilateral CPA tumor. The abnormal HITs in the contralesional direction may be explained either by adaptation or by compression and resultant dysfunction of the cerebellar and brainstem structures. The serial evaluation of HITs may provide information on tumor growth, and thereby reduce the number of costly brain scans required when following up patients with CPA tumors.     

Effect upon eye movements of rabbits induced by severance of mossy fiber visual pathway to the cerebellar flocculus

In albino rabbits the visual mossy fiber pathway to the cerebellar flocculus was interrupted by placing lesions in the nucleus reticularis tegmenti pontis (NRTP). After recovery of more than 3 days, eye movements were tested by means of a television eye tracking system. The optokinetic response (OKR) in one eye induced by sinusoidally moving a vertical slit light on the horizontal plane (2.5° peak-to-peak amplitude) at 0.17-0.033 Hz in front of that eye. In rabbits with unilateral NRTP lesions, the OKR gain was reduced significantly in the eye contralateral to lesions, whereas that in the ipsilateral eye did not differ from control rabbits. The horizontal vestibulo-ocular reflex (HVOR) exhibited no change attributable to NRTP lesions. The operated rabbits were rotated (5° peak-to-peak amplitude) at 0.1 Hz continuously for 3 h, while the slit light was presented to the eye contralateral to the NRTP lesions. During the rotation, the HVOR gain in the test eye increased adaptively as in control rabbits. It is concluded that the visual mossy fiber pathway to the flocculus contributes to the OKR, but not to visually-guided adaptive modification of the HVOR.