Correlation Between IL-10 and microRNA-187 Expression in Epileptic Rat Hippocampus and Patients with Temporal Lobe Epilepsy.

Accumulating evidence is emerging that microRNAs (miRNAs) are key regulators in controlling neuroinflammatory responses that are known to play a potential role in the pathogenesis of temporal lobe epilepsy (TLE). The aim of the present study was to investigate the dynamic expression pattern of interleukin (IL)-10 as an anti-inflammatory cytokine and miR-187 as a post-transcriptional inflammation-related miRNA in the hippocampus of a rat model of status epilepticus (SE) and patients with TLE. We performed a real-time quantitative PCR and western blot on rat hippocampus 2 h, 7 days, 21 days and 60 days following pilocarpine-induced SE, and on hippocampus obtained from TLE patients and normal controls. To detect the relationship between IL-10 and miR-187 on neurons, lipopolysaccharide (LPS) and IL-10-stimulated neurons were performed. Furthermore, we identified the effect of antagonizing miR-187 by its antagomir on IL-10 secretion. Here, we reported that IL-10 secretion and miR-187 expression levels are inversely correlated after SE. In patients with TLE, the expression of IL-10 was also significantly upregulated, whereas miR-187 expression was significantly downregulated. Moreover, miR-187 expression was significantly reduced following IL-10 stimulation in an IL-10-dependent manner. On the other hand, antagonizing miR-187 promoted the production of IL-10 in hippocampal tissues of rat model of SE. Our findings demonstrate a critical role of miR-187 in the physiological regulation of IL-10 anti-inflammatory responses and elucidate the role of neuroinflammation in the pathogenesis of TLE. Therefore, modulation of the IL-10 / miR-187 axis may be a new therapeutic approach for TLE.

miRNAs: biological and clinical determinants in epilepsy.

Recently, microRNAs (miRNAs) are reported to be crucial modulators in the pathogenesis and potential treatment of epilepsies. To date, several miRNAs have been demonstrated to be significantly expressed in the epileptic tissues and strongly associated with the development of epilepsy. Specifically, miRNAs regulate synaptic strength, inflammation, neuronal and glial function, ion channels, and apoptosis. Furthermore, peripheral blood miRNAs can also be utilized as diagnostic biomarkers to assess disease risk and treatment responses. Here, we will summarize the recent available literature regarding the role of miRNAs in the pathogenesis and treatment of epilepsy. Moreover, we will provide brief insight into the potential of miRNA as diagnostic biomarkers for early diagnosis and prognosis of epilepsy.

[Neuronal synaptic reconstruction in hippocampus in chronic phase of pilocarpine-treated rats].

OBJECTIVE: To explore the aberrant formation of excitatory and inhibitory circuit rearrangements of hippocampus in temporal lobe epilepsy. METHODS: Pilocarpine-induced animal model was established. At around Day 60 post-modeling, retrograde tracer fluorogold (FG) was injected in vivo into CA1 and CA3 areas of hippocampus by stereotaxic apparatus. Immunohistochemistry of FG was used to observe the aberrant excitatory circuit rearrangements. Double immunofluorescence with NPY (neuropeptide Y) and FG was performed to observe the aberrant inhibitory circuit rearrangements. RESULTS: After an injection of FG into CA1 area, the FG-labeled pyramidal cells could be observed distantly from the zone of dye spread in CA1 area, CA3 area and subiculm. And the FG-labeled non-principal neurons could be seen in stratum oriens of CA1 and hilus in experimental group. Double immunofluorescence revealed that the FG-labeled NPY interneurons were located distantly from the zone of dye spread in CA1 area, CA3 area and hilus in experimental rats. When injection was administered in CA3 area, the FG-labeled pyramidal cells were visible in the whole CA3 area and hilus in both groups. Some pyramidal cells were present in CA1 in experimental group. Also some FG-labeled non-principle cells were found in hilus and distantly from the zone of dye spread in CA1 area. And the FG-labeled NPY neurons could be seen in hilus in experimental rats. CONCLUSION: Aberrant excitatory and inhibitory synaptic reconstruction exist in hippocampus in chronic phase of temporal lobe epilepsy, including excitatory synaptic connections among pyramidal cells in CA1 area, pyramidal cells between CA1 and subiculum and pyramidal cells between CA1 and CA3, inhibitory synaptic connections among dendritic interneurons in CA1 area, CA3 to CA1, hilus to CA1 and hilus to CA3 area. These circuit arrangements may play an important role in the pathogenesis of epilepsy.

Changes in the numbers and distribution of calretinin in the epileptic rat hippocampus.

OBJECTIVES: To examine calretinin (CR)-containingObjectives: To examine cairetinin (CR)-containingnterneuronsthatdegenerate inthe hippocampus in post statusinterneurons that dege nera te in the hippocampusepilepticus (SE) ratsatdifferent time in post status epilepticus (SE) rats at different time points. METHODS: This study was conducted at the Central South University, Xiangya Hospital, Hunan Province, P.R. China between September 2008 and January 2010. Pilocarpine-induced SE was chosen as a model to generate chronic epileptic rats. To determine whether hippocampal neuronal populations are affected by hippocampal seizures, immunohistochemical assays were performed in brain sections obtained from age-matched control (n=50) and epileptic rats (n=170). Nissl stain was used to observe pathological changes of the hippocampus. RESULTS: Our results revealed the most dramatic cell loss to be in the hilar, cornu Ammonis (CA)1, and CA3 areas in the epileptic rats. Quantitative analysis revealed significant differences between control and epileptic rats in the number of CR-positive interneurons. These interneurons were distributed in the hilar, CA1, and CA3 areas and in thedentate gyrus of both control and epileptic rats, but was more numerous in the hippocampus of normal rats. However, a transient increase of CR-positive interneurons was observed in the CA1 between 7 and 15 days post SE. The CR interneurons were mostly located in the hilar and CA1 for epileptic rats, and in the hilus for control rats. CONCLUSIONS: Our data suggest that a different proportion of inhibitory interneurons was observed in the epileptic rat hippocampus, as their numbers differ from controls. These results indicate that the inhibitory circuits in the hippocampus may represent a compensatory response with a role to balance the enhanced excitatory input in the region.

Use of urokinase in the treatment of tuberculous meningitis hydrocephalus.

We present a patient with hydrocephalus after tuberculous meningitis successfully treated with urokinase. She presented with multiple episodes of headache, fever, and vomiting. She underwent external ventricular drainage and was treated with urokinase in addition to dexamethasone, acetazolamide, and 4 antituberculous drugs. She was evaluated clinically, radiologically, and by laboratory work-up. On short-term clinical follow-up (3 months), she was asymptomatic after the treatment with urokinase. She was radiologically evaluated 3 weeks after the treatment. An MRI of the brain showed a decrease in ventricular size. Urokinase can be considered as a safe and promising adjunctive treatment for tuberculous meningitis hydrocephalus.

Experimental epileptic discharge can be transmitted between 2 brains in rats.

OBJECTIVE: To identify whether epileptic discharges can be conducted out of the brain according to the principle of a lightning rod. METHODS: This experimental study was conducted at Central South University, Xiangya Hospital, Hunan, China between 2005 and 2008. Eighty Sprague-Dawley rats were implanted with intra hippocampus and intra frontal lobe electrodes, and randomized to 3 groups: (A) a group that was kindled via stimulation of intra-hippocampus injection of penicillin, (B) a group that was stimulated via a copper wire connected to the intra-hippocampus electrodes of group A, (C) a group composed of non-stimulated, control rats. The behavioral changes and epileptiform activity were assessed by both Racine Grade and electrocorticogram (ECoG). RESULTS: The intrahippocampal ECoG recordings were coincident with clinical seizures, electrographic seizures occurred not only in the injected hippocampus group A rats, but also in the connected group B rats. However, there were no visible seizures or ECoG burst at any time in group C rats. CONCLUSION: Epileptic discharge can be conducted out of the brain, which may open new therapeutic approaches for epilepsy.

Comparison between solitary and multiple intracranial tuberculoma.

OBJECTIVE: To compare and analyze the clinical, radiological, and pathological features of solitary or/and multiple CNS tuberculomas (CNSTs). METHODS: The study was conducted at Central South University, First Xiangya Hospital, Changsha, Hunan, China between 1998-2008. Forty-two subjects with diagnosed CNSTs were compared and analyzed by multiple or solitary lesions seen on enhanced MRI. The final diagnosis of tuberculomas was confirmed by histopathology. RESULTS: From the 42 subjects, 64.3% multiple CNSTs were observed, out of which, 55.6% were with meningitis and 44.4% without meningitis. Of the CNSTs, solitary lesions were present in 35.7%, 80% of which were without meningeal involvement, and 20% with meningeal involvement. In multiple CNSTs, 55.6% were noncaseating granulomas, and 74.1% caseating granulomas with a solid center, while in solitary CNSTs, 80% were caseating granulomas with a solid center. For multiple lesions, temporal lobe, frontal lobe, cerebella, and brain stem were predilection sites. While for solitary lesions, apical lobe, and cerebellum were predilection sites. The histopathological features were the same in all multiple and solitary lesions. CONCLUSION: Multiple CNSTs are more often associated with meningitis, while solitary CNSTs particularly occur with less or atypical clinical manifestation. Difference in the predilection sites between multiple and solitary CNSTs were observed.