It is well known that the status epilepticus induced by the administration of pilocarpine to lithium-pretreated rats is a role model to study for the cholinergic system in epileptogenesis and the pathogenesis of status epilepticus. Although the researches for the expression of the c-fos proto-oncogene in seizure models have been studied, the exact role of the c-fos expression is still uncertain. To evaluate the characteristics of lithium-pilocarpine seizure model, we designed this study by following three steps; (1) the analysis of clinical manifestations by video, and electroencephalogram through implanted cortical electrodes during the course of status epilepticus induced by intraperitoneal administration of lithium chloride (5 mEq/kg) followed by pilocarpine(50 mg/kg) in Sprague-Dawley rats, (2) Fos expression and the time course of Fos appearance by the immunocytochemistry, (3) Neuropathologic change by cresyl violet stain. The presentation of clinical manifestations were cholinergic symptoms and signs, stereotyped behaviour, motor seizures, and status epilepticus in order. Electroencephalographic findings showed five patterns : (I) discrete seizure with interictal slowing; (ii) merging seizures with waxing and waning ictal discharges; (iii) continuous ictal discharges; (iv) continuous ictal discharges with flat periods; and (v) periodic epileptiform discharges on a flat background. The neuroanatomical sites of Fos expression were the taenia recta, anterior olfactory nucleus, olfactory tubercle, piriform cortex, entorhinal cortex, amygdala, septum, accumbens, caudate-putamen, hippocampus, dentate gyrus, thalamus, and cerebral neocortex. The Fos immunostaining appeared first in the taenia tecta, anterior olfactory nucleus, olfactory tubercle, and piriform cortex at 1 hour after pilocarpine injection, and was maximal in the most areas of cerebral cortex and limbic area between 4 and S hours. The thalamus and the caudate-putamen became stained after 4 hours. In the hippocampal formation, firstly, the Fos was stained maximally in the dentate gyrus at 3 hours followed by in the CA1, CA2, and CA3 regions. The Fos was disappeared in the dentate gyrus and CA2 region of hippocampus within 18 hours, but became stained sustainly in the CA3 and CA1 regions of hippocampus at 24 hours. Llght microscopic findings revealed widespread brain damage. The neuropathological changes were found within the anterior olfactory nucleus, piriform cortex, entorhinal cortex, thalamus, hippocampal formation, amygdaloid complex, lateral septum, neocortex and substantia nigra. There were only swollen and edematous change of neurons at 1 hour, but severely shrunken and darkened neuronal degeneration and neuronal loss at 72 hours. The neuronal degeneration and loss in hippocampal formation appeared severe in the CA1 and hilum, moderate in CA2, and mild in CA3 and dentate gyrus. In conclusion, it was suggested that cholinergic system (muscarinic receptor) played an important role in the induction of the seizure because Fos was expressed in the brain areas containing muscarinc receptor and the lithium-pilocarpine seizure was a good model to study for the status epilepticus.
Amygdala ; Animals ; Brain ; Cerebral Cortex ; Dentate Gyrus ; Electrodes ; Electroencephalography* ; Entorhinal Cortex ; Genes, fos ; Hippocampus ; Immunohistochemistry ; Lithium Chloride ; Neocortex ; Neurons ; Olfactory Pathways ; Pilocarpine ; Rats ; Rats, Sprague-Dawley ; Seizures* ; Status Epilepticus ; Substantia Nigra ; Taenia ; Thalamus ; Viola

Intranasal administration provides a method of bypassing the blood brain barrier, which separates the systemic circulating system and central interstitial fluid, and directly delivering drugs to the central nervous system. This method also circumvents first-pass elimination by the liver and gastrointestinal tract. In the present study, the authors investigated intranasal siRNA delivery efficiency by using FITC-labeled transfection control siRNA and a genespecific siRNA. The localization of fluorescence-tagged siRNA revealed that siRNA was delivered to cells in the olfactory bulb and that the level of the siRNA target gene (alpha B-crystallin) was significantly reduced in the same area. siRNA was delivered to processes as well as nuclei and cytoplasm. At 12 hrs after intranasal delivery, siRNA-mediated target gene reduction was observed in other more distally located brain regions, for example, in the amygdala, entorhinal cortex, and hypothalamus. Target gene knockdown was demonstrated by double immunohistochemistry, which demonstrated alpha B crystallin expression depletion in more than 70% of cells at 12 hrs after the intranasal delivery. siRNA-mediated target gene suppression was detected not only in neurons but in glia, for example, astrocytes. These results indicate that intranasal siRNA delivery offers an efficient means of reducing specific target genes in certain regions of the brain and of performing gene knockdown-mediated therapy.
Administration, Intranasal ; alpha-Crystallin B Chain ; Amygdala ; Astrocytes ; Blood-Brain Barrier ; Brain ; Central Nervous System ; Cytoplasm ; Entorhinal Cortex ; Extracellular Fluid ; Gastrointestinal Tract ; Gene Knockdown Techniques ; Hypothalamus ; Immunohistochemistry ; Liver ; Neuroglia ; Neurons ; Olfactory Bulb ; RNA, Small Interfering ; Transfection

OBJECTIVETo analyze the correlation between olfactory bulb(OB) volume with depth of olfactory sulcus (OS) and olfactory function in patients with idiopathic olfactory loss (IOL).

METHODSForty patients with IOL and forty normal controls were compared in terms of olfactory function T&T testing and magnetic resonance imaging (MRI, observation of OB volume and depth of OS). T&T testing and MRI were performed again after a year in 40 IOL patients, the results were compared with the first time.

RESULTSOB volume of left side in IOL patients was (30.31 ± 4.07) mm(3), right side was (30.82 ± 4.14) mm(3), average OB volume was (30.53 ± 4.10) mm(3); OB volume of left side in normal controls was (49.56 ± 7.19) mm(3), right side was (49.84 ± 7.25) mm(3), average OB volume was (49.73 ± 7.21) mm(3). OB volume was lower in IOL patients as compared to controls (t value were 8.122, 8.274, 8.231, all P < 0.01). OS depth study revealed no statistical different between IOL patients and controls (t value were 0.998, 1.017, 1.001, all P > 0.05). Olfactory discriminate threshold was negatively correlated with OB volume in IOL patients (r = -0.53, P < 0.05). There was no correlation with the depth of OS (r = -0.19, P > 0.05). Among 40 IOL patients, when followed-up, 12 showed increased in OB volume and olfactory function after a year, but no statistical difference was found with the first time (t value were 0.831, 0.864, 0.826, all P > 0.05). The other 28 patients showed no significant changes of OB volume and olfactory function.

CONCLUSIONSThe OB volume was lower in IOL patients as compared to normal controls. The depth of OS showed no significant changes in IOL patients. The OB volume was correlated with olfactory function. The depth of OS did not correlated with the olfactory function. Some IOL patients showed increased OB volume and improved olfactory function with the development of the disease.

Humans ; Magnetic Resonance Imaging ; Olfaction Disorders ; diagnosis ; Olfactory Bulb ; anatomy & histology ; Prefrontal Cortex ; anatomy & histology ; Smell

OBJECTIVETo explore the brain activation before and in early period after olfactory adaptation using functional magnetic resonance imaging, and discuss the mechanisms of olfactory adaptation.

METHODSTen right-handed, normosmic subjects underwent 2 times of olfactory stimulation tasks with the interval of 20 minutes. The odorant used was isovaleric acid. The fMRI data was processed by the SPM5 software. Rating odor intensity and valence using visual analogue scale (VAS), and the results of 2 tasks were statistically analyzed.

RESULTSThere was no significant difference between 2 tasks on both intensity and hedonicity scores. In task 1, the brain activation in bilateral cerebellum, frontal (including orbitofrontal gyrus), insula, thalamus, cingulate gyrus, putamen, amygdala, piriform cortex, the left inferior parietal lobule, precentral gyrus, right hippocampus, pallidum, middle temporal gyrus, supramarginal gyrus. In task 2, only the right middle frontal gyrus activated, and the voxels decreased significantly. Paired t-test results showed that: (task1-task2) activated regions in left precentral gyrus, frontal lobe (including the orbitofrontal gyrus), insula, right superior temporal gyrus, cerebellum; (task2-task1) activation in the left inferior parietal lobule and right lingual gyrus.

CONCLUSIONSThe sensitivity of brain activation is still at a low level, when subjects had recovered from adaptation in subjective olfactory perception. Underwent repeated olfactory stimulation, second olfactory cortex plays less role on olfactory perception and advanced processing.

Adaptation, Physiological ; Adult ; Cerebral Cortex ; physiology ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Olfactory Perception ; physiology

OBJECTIVETo analyze the correlation between olfactory bulb (OB) volume, depth of olfactory sulcus (OS) and olfactory function in patients with olfactory dysfunction after upper respiratory tract infection.

METHODSOne hundred patients with olfactory dysfunction after upper respiratory tract infection (patient group) were compared with one hundred normal controls in terms of olfactory function T&T testing, OB volume and depth of OS assessed with magnetic resonance imaging (MRI). T&T testing and MRI were performed again after a year in patient group and the results were compared. SPSS 13.0 software was used to analyze the data.

RESULTST&T olfactory testing revealed that the patient group had higher scores than controls (t = 4.014, P < 0.05). Both men and women in patient group were affected by the same extent of olfactory loss (t value was 0.892, P > 0.05). Both men and women in control group were affected by the same extent of olfactory loss (t value was 1.011, P > 0.05). OB volume of left side in patient group was (38.14 ± 4.31) mm³, right side was (38.72 ± 4.22) mm³, average OB volume was (38.47 ± 4.27) mm³; OB volume of left side in controls was (51.65 ± 6.30) mm³, right side was (51.98 ± 6.34) mm³, average OB volume was (51.81 ± 6.32) mm³; OB volume was lower in patient group as compared with controls (t value were 4.233, 4.267 and 4.249, all P < 0.01). OS depth study revealed no statistical difference between patient group and control group (t value were 0.901, 0.948 and 0.927, all P > 0.05). Olfactory discriminate threshold was negatively correlated with OB volume in patient group and control group (r value were -0.598, -0.512, both P < 0.05) Olfactory discriminate threshold was not correlated with the depth of OS (r value were -0.152, -0.174, both P > 0.05). Olfactory discriminate threshold and OB volume were not correlated with the persistent time of the dysosmia in patient group (r value were -0.121, 0.139, both P > 0.05). Among 100 olfactory dysfunction patients after upper respiratory tract infection, when followed-up, 24 showed increased in OB volume and olfactory function after a year, but no statistical difference was found with the first time (t value were 0.894, 0.914, 0.942 and 0.931, all P > 0.05). The other 76 patients showed no significant changes of OB volume and olfactory function.

CONCLUSIONSThe OB volume was lower in patient group as compared with normal controls, the depth of OS showed no significant changes in patient group. The OB volume was correlated with olfactory function, the depth of OS was not correlated with olfactory function; Olfactory function had not correlated with the persistent time of the dysosmia in patient group.

Female ; Humans ; Magnetic Resonance Imaging ; Male ; Olfaction Disorders ; diagnosis ; Olfactory Bulb ; pathology ; Prefrontal Cortex ; pathology ; Respiratory Tract Infections ; physiopathology

OBJECTIVE: To explore the olfactory abilities in patients with allergic rhinitis (AR), analyze the correlation between olfactory bulb (OB) volume with depth of olfactory sulcus (OS) and olfactory function in patients with AR. METHOD: One hundred patients with AR were compared with one hundred controls in terms of olfactory function T&T testing, OB volume and depth of OS assessed with magnetic resonance imaging (MRI). T&T testing and MRI were done after a year in 100 AR patients,the results were compared with the initial results. RESULT: The OB volume in AR patients was (29.53±3.95) mm3 on the left, (29.67±14.21)mm3 on the right, (29.61±4.05) mm3 on average; The OB volume in controls was (48.93±6.73)mm3 on the left side, (48.81±7.43)mm3 on the right side, (48.85±7.11)mm3 on average; The OB volume in AR patients was less then the control group(t= 6.321, 6.141, 6.221, P<0.01). The OS depth had no statistical difference between AR patients and controls (t=1.032, 0.972, 0.991, P>0.05). Olfactory discriminate threshold was negatively correlated with OB volume in AR patients (r=-0.46, P<0.05); and it was no correlated with depth of OS (r=-0.012,P>0.05). Among 100 followed-up AR patients, 43 showed increased in OB volume and olfactory function after a year, but there was no statistical difference (t= 0. 811,0. 843, 0.826, P>0.05; Z=1.911, P>0.05) ,and the other 57 showed no significant changes of OB volume and olfactory function. CONCLUSION In AR patients, the OB volume and olfactory function decreased, but the depth of OS had no significant changes. The OB volume is correlated with olfactory function, while the depth of OS is no correlated with olfactory function. Conservative treatment had some clinical significance on the recovery of olfactory function in patients with AR.
Humans ; Magnetic Resonance Imaging ; Olfaction Disorders ; etiology ; Olfactory Bulb ; pathology ; physiopathology ; Prefrontal Cortex ; Rhinitis, Allergic ; complications ; Smell

The frontal cortex of rat is innervated by dopaminergic pathway(mesocortical pathway) arising from ventral tegmental area. Several studies have suggested that mesocortical dopaminergic neurons may modulate the function of dopaminergic neurons at subcortical sites. The effect of lesions of the dopaminergic nerve terminals in the medial prefrontal cortex of the rat on dopamine D1 and D2 receptors within the striatum and olfactory tubercle has been investigated. Bilateral 6-hydroxy-dopamine lesions were stereotaxically placed in the medial prefrontal cortex. Animal were pretreated with desipramine to block the uptake of neurotoxin into noradrenergic terminals and to make it more selective for dopamine terminal. After 2weeks later, we examined the changes of D1 and D2 receptors in caudate-putamen and nucleus accumbens by quantitative autoradiography using the specific D1 antagonist [3H]SCH23390 and D2 antagonist [3H]spiperone. The results shows that D1 receptor at striatum was up regulated 2weeks after destruction of dopamine terminals within medial prefrontal vortex of the rat. This findings suggest that frontal cortical dopamine system may regulate the dopamine system in corpus striatum.
Animals ; Autoradiography ; Corpus Striatum ; Desipramine ; Dopamine* ; Dopaminergic Neurons ; Nucleus Accumbens ; Olfactory Pathways ; Oxidopamine* ; Prefrontal Cortex* ; Rats* ; Receptors, Dopamine* ; Ventral Tegmental Area

OBJECTIVES: Peripheral benzodiazepine receptor has been suggested to be associated with the relief of anxiety response induced by stresses. This study was designed to observe the anxiolytic activity of peripheral benzodiazepine receptor. METHODS: Male Sprague-Dawley rats, weighing 200-250g were forced to suffer an immobilization stress for 2 hours. The level of anxiety by immobilization was performed by an elevated plus maze and was evaluated by the number of [3H]Ro5-4864 binding sites in the olfactory bulb. RESULTS: Saturation experiments followed by scatchard anlayses of the results showed that the density of peripheral benzodiazepine receptor increased and the affinity of the peripheral benzodiazepine receptor remained unchanged. It was found that there was no significant change in the cerebral cortex. Pretreatment with clonazepam, a central benzodiazepine receptor agonist, before an immobilization stress abolished the anxoius response on the performance of plus maze. In this group, upregulation of peripheral benzodiazepine receptor of olfactory bulb was not observed. Ro5-4864, a peripheral benzodiazepine receptor agonist, elicited an increase of anxiolytic response on the performance of plus maze. Progesterone, a precursor of neuroactive steroid, also increased anxiolytic response on the performance of plus maze. Pretreatment with PK11195, a peripheral benzodiazepine receptor antagonist, abolshed the anxiolytic effect of progesterone. CONCLUSIONS: From these results, it could be concluded that peripheral benzodiazepine receptor is closely associated with the relief of acute stress induced anxiety response via an increase of synthesis of neuroactive steroid.
Animals ; Anti-Anxiety Agents ; Anxiety* ; Benzodiazepines* ; Binding Sites ; Cerebral Cortex ; Clonazepam ; Humans ; Immobilization ; Male ; Olfactory Bulb ; Progesterone ; Rats* ; Rats, Sprague-Dawley ; Receptors, GABA-A* ; Up-Regulation

We investigated a topographical distribution of managanese, and immunohistochemical density of tyrosine hydroxylase (TH), and histopathologic findings in globus pallidus and substantia nigra according to manganese dose and time course in the brain of rats which received MnCl2 intravenously. Topographical distribution of manganese was also investigated after injection of FeCl2. The manganese concentrations of brain in control and experimental group were highest in pituitary gland and thalamus, and lowest in the cerebral cortex. The manganese concentration of blood was increased proportionally to the dose administered, and the biological half-life of blood manganese was between 21 and 42 days. The manganese concentrations of brain were increased proportionally to the dose, and increase rate was highest in olfactory bulb, and the biological half-lives of brain manganese ranged from 42 days to 90 or more days; the longest were observed in pituitary gland, medulla oblongata and cerebral cortex. In case of administration of FeCl2, the manganese concentrations of brain were higher than that of control group in dose of 2.5 mg/kg, and decreased proportionally to the administered dose, resulting in lower level compared with control group in high dose of FeCl2 administered. Significantly decreased number of nerve cell and increased gliosis in globus pallidus were observed in experimental group, which were closely correlated with the duration after manganese injection, but no significant change of number of nerve cell expressing TH and gliosis were observed in substantia nigra. Density of immunohistochemical reaction for TH in globus pallidus made little difference between control and experimental group. These results suggest that pathology of manganese intoxication is caused by the loss of nerve cells in globus pallidus, and closely correlated with the duration after manganese exposure.
Animals ; Brain* ; Cerebral Cortex ; Gliosis ; Globus Pallidus ; Half-Life ; Manganese* ; Medulla Oblongata ; Neurons ; Olfactory Bulb ; Pathology ; Pituitary Gland ; Rats* ; Substantia Nigra ; Thalamus ; Tyrosine 3-Monooxygenase

The Kallmanns syndrome is the most common form of isolated hypogonadotropic hypogonadism in which anosmia or hyposmia resulting from agenesis of hypoplasia of the olfactory lobes is associated with LHRH deficiency, This syndrome is genetically heterogeneous and can be trans-mitted as an X-linked, autosomal dominant or autosomal recessive trait. The hypogonadotropic hypogonadism results in absent or incomplete pubertal development and may be associated with anosmia or hyposmia, mid-line defect(color blindness, cleft-lip or
Blindness ; Cryptorchidism ; Epiphyses ; Femur Neck ; Gonadotropin-Releasing Hormone ; Growth Plate ; Head ; Humans ; Hypogonadism ; Kallmann Syndrome ; Male ; Olfaction Disorders ; Olfactory Cortex ; Slipped Capital Femoral Epiphyses