BACKGROUND: Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model. METHODS: Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups. RESULTS: ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001). CONCLUSION ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.
Adenosine Monophosphate ; Anterior Thalamic Nuclei ; Cyclic AMP-Dependent Protein Kinases ; Deep Brain Stimulation ; Epilepsy/therapy* ; Epilepsy, Temporal Lobe/therapy* ; Hippocampus ; Humans ; Mossy Fibers, Hippocampal ; Signal Transduction

The artery of Percheron (AOP) is an uncommon variant of the paramedian artery, a solitary trunk branching off from the posterior cerebral arteries, supplying both paramedian thalami, and also often the rostral midbrain and the anterior thalamus. The typical clinical manifestations of the AOP infarction include altered mental status, cognitive impairment, and oculomotor dysfunction. We report a rare case with AOP infarction, and the clinical characteristics and rehabilitation courses for alertness disorder, cognitive dysfunction, and other accompanied symptoms.
Anterior Thalamic Nuclei ; Arteries* ; Cognition ; Cognition Disorders ; Infarction* ; Mesencephalon ; Ophthalmoplegia ; Posterior Cerebral Artery ; Rehabilitation ; Thalamus

BACKGROUNDThe antiepileptic effect of the anterior thalamic nuclei (ANT) stimulation has been demonstrated; however, its underlying mechanism remains unclear. The aim of this study was to investigate the effect of chronic ANT stimulation on hippocampal neuron loss and apoptosis.

METHODSSixty-four rats were divided into four groups: The control group, the kainic acid (KA) group, the sham-deep brain stimulation (DBS) group, and the DBS group. KA was used to induce epilepsy. Seizure count and latency to the first spontaneous seizures were calculated. Nissl staining was used to analyze hippocampal neuronal loss. Polymerase chain reaction and Western blotting were conducted to assess the expression of caspase-3 (Casp3), B-cell lymphoma-2 (Bcl2), and Bcl2-associated X protein (Bax) in the hippocampal CA3 region. One-way analysis of variance was used to determine the differences between the four groups.

RESULTSThe latency to the first spontaneous seizures in the DBS group was significantly longer than that in the KA group (27.50 ± 8.05 vs. 16.38 ± 7.25 days, P = 0.0005). The total seizure number in the DBS group was also significantly reduced (DBS vs. KA group: 11.75 ± 6.80 vs. 23.25 ± 7.72, P = 0.0002). Chronic ANT-DBS reduced neuronal loss in the hippocampal CA3 region (DBS vs. KA group: 23.58 ± 6.34 vs. 13.13 ± 4.00, P = 0.0012). After chronic DBS, the relative mRNA expression level of Casp3 was decreased (DBS vs. KA group: 1.18 ± 0.37 vs. 2.09 ± 0.46, P = 0.0003), and the relative mRNA expression level of Bcl2 was increased (DBS vs. KA group: 0.92 ± 0.21 vs. 0.48 ± 0.16, P = 0.0004). The protein expression levels of CASP3 (DBS vs. KA group: 1.25 ± 0.26 vs. 2.49 ± 0.38, P < 0.0001) and BAX (DBS vs. KA group: 1.57 ± 0.49 vs. 2.80 ± 0.63, P = 0.0012) both declined in the DBS group whereas the protein expression level of BCL2 (DBS vs. KA group: 0.78 ± 0.32 vs. 0.36 ± 0.17, P = 0.0086) increased in the DBS group.

CONCLUSIONSThis study demonstrated that chronic ANT stimulation could exert a neuroprotective effect on hippocampal neurons. This neuroprotective effect is likely to be mediated by the inhibition of apoptosis in the epileptic hippocampus.

Animals ; Anterior Thalamic Nuclei ; physiology ; Apoptosis ; Deep Brain Stimulation ; Epilepsy ; pathology ; therapy ; Hippocampus ; pathology ; Kainic Acid ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Seizures ; prevention & control

BACKGROUNDRecent clinical and preclinical studies have suggested that deep brain stimulation (DBS) can be used as a tool to enhance cognitive functions. The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit, including the anterior nucleus of thalamus (ANT), the entorhinal cortex (EC), and the fornix (FX), on cognitive behaviors in an Alzheimer's disease (AD) rat model.

METHODSForty-eight rats were subjected to an intrahippocampal injection of amyloid peptides 1-42 to induce an AD model. Rats were divided into six groups: DBS and sham DBS groups of ANT, EC, and FX. Spatial learning and memory were assessed by the Morris water maze (MWM). Recognition memory was investigated by the novel object recognition memory test (NORM). Locomotor and anxiety-related behaviors were detected by the open field test (OF). By using two-way analysis of variance (ANOVA), behavior differences between the six groups were analyzed.

RESULTSIn the MWM, the ANT, EC, and FX DBS groups performed differently in terms of the time spent in the platform zone (F(2,23) = 6.04, P < 0.01), the frequency of platform crossing (F(2,23) = 11.53, P < 0.001), and the percent time spent within the platform quadrant (F(2,23) = 6.29, P < 0.01). In the NORM, the EC and FX DBS groups spent more time with the novel object, although the ANT DBS group did not (F(2,23) = 10.03, P < 0.001). In the OF, all of the groups showed a similar total distance moved (F (1,42) = 1.14, P = 0.29) and relative time spent in the center (F(2,42) = 0.56, P = 0.58).

CONCLUSIONSOur results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently than ANT DBS. In addition, hippocampus-independent recognition memory was enhanced by EC and FX DBS. None of the targets showed side-effects of anxiety or locomotor behaviors.

Alzheimer Disease ; physiopathology ; therapy ; Animals ; Anterior Thalamic Nuclei ; physiology ; Deep Brain Stimulation ; methods ; Entorhinal Cortex ; physiology ; Fornix, Brain ; physiology ; Male ; Memory ; physiology ; Rats ; Rats, Sprague-Dawley ; Spatial Learning ; physiology

BACKGROUNDThe advent of brain stimulation techniques to treat movement disorders and psychiatric diseases has shown potential to decode the neural mechanism that underlies the cognitive process by modulating the interrupted circuit. Here, the present investigation aimed at evaluating the influence of deep brain stimulation of the anterior nucleus thalamus (ANT-DBS) on memory.

METHODSThirty-two rats were randomized into phosphate buffer saline (PBS) group (n = 8, rats received PBS injections without implantation of electrodes into the ANT), Alzheimer's dementia (AD) group (n = 8, rats received Aβ1-40 injections without implantation of electrodes into the ANT), ANT sham stimulation group (n = 8, rats received Aβ1-40 injections with implantation of electrodes into the ANT but without stimulation) and ANT stimulation group (n = 8, rats received Aβ1-40 injections with implantation of electrodes into the ANT and stimulation). A Morris maze test was used for determining the effect of electrical stimulation on cognitive function in rats. The data were assessed statistically with one-way analysis of variance (ANOVA) followed by Tukey's tests for multiple post hoc comparisons.

RESULTSThe data showed that in the training test, PBS group and AD group managed to learn the hidden-platform faster and faster while AD group needed a significantly longer time to reach the platform than PBS group (P < 0.05). Meanwhile, ANT stimulation group demonstrated a significantly shorter time to reach the platform (P < 0.05) compared to the AD group, while there was no significant difference between the ANT sham stimulation group and the AD group (P > 0.05). On the probe test, the AD group spent less time ((10.15 ± 2.34) seconds) in the target quadrant than the PBS group ((28.20 ± 2.75) seconds) (P < 0.05). And the times of platform-traversing of the AD group (3.35 ± 1.12) significantly decreased compared with the PBS group (8.69 ± 2.87) (P < 0.05). However, the times of platform-traversing and the time spent in the target quadrant of the ANT stimulation group significantly increased compared to the AD group (P < 0.05), while times of platform-traversing or the time spent in the target quadrant was not significantly different between the ANT sham stimulation group and the AD group (P > 0.05).

CONCLUSIONBilateral high-frequency stimulation of the ANT may be useful as a potential therapeutic modality for cognitive dysfunction in AD.

Amyloid beta-Peptides ; administration & dosage ; toxicity ; Animals ; Anterior Thalamic Nuclei ; drug effects ; Cognition ; drug effects ; Cognition Disorders ; chemically induced ; therapy ; Deep Brain Stimulation ; methods ; Hippocampus ; drug effects ; Male ; Peptide Fragments ; administration & dosage ; toxicity ; Rats ; Rats, Sprague-Dawley

BACKGROUNDElectrical stimulation of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures. In this study, we investigated changes in glucose metabolism during high-frequency stimulation of ANT in epileptic rats.

METHODSThree groups of rats were used: (1) a stimulation group (n = 12), (2) a sham stimulation group (n = 12) with seizures induced by stereotactic administration of kainic acid (KA), and (3) a control group (n = 12) with sham surgery. Concentric bipolar electrodes were stereotaxically implanted unilaterally in the ANT. High-frequency stimulation was performed in each group except the sham stimulation group. Microdialysis probes were lowered into the CA3 region of the hippocampus unilaterally but bilaterally in the stimulation group. The concentrations of glucose, lactate, and pyruvate in dialysate samples were determined by an ISCUS microdialysis analyzer.

RESULTSThe extracellular concentrations of lactate and lactate/pyruvate ratio (LPR) of epileptic rats were significantly higher than in control rats (P = 0.020, P = 0.001; respectively). However, no significant difference in the concentration of glucose and pyruvate was found between these groups (P > 0.05). Electrical stimulation of ANT induced decreases in lactate and LPR in the ipsilateral hippocampus (KA injected) of the stimulation group (P < 0.05), but it did not influence the glucose metabolism in the contralateral hippocampus (P > 0.05).

CONCLUSIONSThis study demonstrated that the glycolysis was inhibited in the ipsilateral hippocampus of epileptic rats during electrical ANT stimulation. These findings may provide useful information for better understanding the mechanism of ANT-deep brain stimulation.

Animals ; Anterior Thalamic Nuclei ; physiology ; Deep Brain Stimulation ; Epilepsy ; metabolism ; therapy ; Glucose ; metabolism ; Glycolysis ; Hippocampus ; metabolism ; Male ; Rats ; Rats, Wistar

It has been suggested that epileptic seizures can be interrupted by deep brain stimulation (DBS) of various deep brain structures which may exert a therapeutic control on seizure generators or correspond to ictal onset zone themselves. Several groups have used DBS in drug-resistant epilepsy cases for which resective surgery cannot be applied. The promising subcortical brain structures are anterior and centromedian nucleus of the thalamus, subthalamic nucleus, and other nuclei to treat epilepsy in light of previous clinical and experimental data. Recently two randomized trials of neurostimulation for controlling refractory epilepsy employed the strategies to stimulate electrodes placed on both anterior thalamic nuclei or near seizure foci in response to electroencephalographically detected epileptiform activity. However, the more large-scale, long-term clinical trials which elucidates optimal stimulation parameters, ideal selection criteria for epilepsy DBS should be performed before long.
Anterior Thalamic Nuclei ; Brain ; Deep Brain Stimulation ; Electrodes ; Epilepsy ; Intralaminar Thalamic Nuclei ; Light ; Patient Selection ; Seizures ; Subthalamic Nucleus ; Thalamus

PURPOSE: To evaluate the MR imaging findings of patients with mesial temporal sclerosis. MATERIALS AND METHODS:We retrospectively reviewed the MR imaging findings of 116 patients diagnosed by MRI as suffering from mesial temporal sclerosis. In 18 of these, the condition was also histologically proven. RESULTS: Among the 116 patients, volume loss of the hippocampus was found in 95 (81.9%) and signal changes of the hippocampus in 53 (45.7%). Decreased signal intensity in the hippocampus on T1-weighted images was found in 13 (11.2%) and increased signal on T2-weighted images in 50 (43.1%). Signal abnormality in the hip-pocampus on both T1- and T2-weighted images was found in ten, and associated extrahippocampal abnormali-ties, as follows, in 20 (17.2%): atrophy of the fornix (n=10), atrophy of the mammillary body (n=8), atrophy of the amygdala (n=10), atrophy or increased T2 signal intensity of the anterior thalamic nuclei (n=2), atrophy of the cingulate gyrus (n=2), atrophy or increased signal intensity of the anterior temporal lobe (n=8), and cere-bral hemiatrophy (n=4). CONCLUSION: A high T2 signal and atrophy of the hippocampus are the most common and important MRI findings of mesial temporal sclorosis. Other abnormal findings, if any, which may be found in extrahippocampal structures such as the fornix, mammillary body and temporal lobe, should, however, also be carefully observed
Amygdala ; Anterior Thalamic Nuclei ; Atrophy ; Epilepsy ; Gyrus Cinguli ; Hippocampus ; Humans ; Magnetic Resonance Imaging* ; Mamillary Bodies ; Retrospective Studies ; Sclerosis* ; Temporal Lobe

This experimental studies was to investigate the location of CNS labeled neurons following injection of pseudorabies virus (PRV), Bartha strain, into the rat thymus. After survival times of 96~120 hours following injection of PRV, the rats were perfused, and their spinal cord and brain were frozen sectioned(30micrometer). These sections were stained by PRV immunohistochemical staining method, and observed with light microscope The results were as follows: 1. The PRV labeled spinal cord segments projecting to the rat thymus were founded in cervical and thoracic segments. Densely labeled areas of each spinal cord segment were founded in lamina V, VII, X, intermediolateral nucleus and dorsal nucleus. 2. In the rhombencephalon, PRV labeled neurons projecting to the thymus were founded in the A1 noradrenalin cells/C1 adrenalin cells/caudoventrolateral reticular nucleus, rostroventro-lateral reticular nucleus, medullary reticular nucleus, area postrema, nucleus solitary tract, nucleus raphe obscurus, nucleus raphe pallidus, nucleus raphe magnus, gigantocellular reticular nucleus, lateral paragigantocellular nucleus and spinal trigeminal nucleus. 3. In the mesencephalon, PRV labeled neurons were founded in parabrachial nucleus, Kolliker-Fuse nucleus, central gray matter, substantia nigra, nucleus dorsal raphe, A8 dopamin cells of retrorubral field, Edinger-Westphal nucleus, locus coeruleus, subcoeruleus nucleus and A5 noradrenalin cells. 4. In the prosencephalon, PRV labeled neurons were founded in reuniens thalamic nucleus, paraventricular thalamic nucleus, precommissural nucleus, paraventricular hypothalamic nucleus, anterior hypothalamic nucleus, lateral hypothalamic nucleus, preoptic hypothalamic nucleus, retrochiasmatic area, arcuate nucleus, dorsomedial hypothalamic nucleus and ventromedial hypothalamic nucleus. These results suggest that PRV labeled neurons of the spinal cord projecting to the rat thymus might be the neurons related to the viscero-somatic sensory and sympathetic preganglionic neurons, and PRV labeled neurons of the brain may be the neurons response to the movement of smooth muscle in blood vessels. These PRV labeled neurons may be central autonomic center related to the integration and modulation of reflex control linked to the sensory system monitoring the internal environment. These observations provide evidence for previously unknown projections from spinal cord and brain to the thymus which may be play an important role in the regulation of thymic function.
Animals ; Anterior Hypothalamic Nucleus ; Arcuate Nucleus ; Area Postrema ; Blood Vessels ; Brain ; Dorsomedial Hypothalamic Nucleus ; Herpesvirus 1, Suid* ; Hypothalamic Area, Lateral ; Immunohistochemistry ; Locus Coeruleus ; Mesencephalon ; Midline Thalamic Nuclei ; Muscle, Smooth ; Neurons* ; Paraventricular Hypothalamic Nucleus ; Prosencephalon ; Pseudorabies* ; Rats* ; Reflex ; Rhombencephalon ; Spinal Cord ; Substantia Nigra ; Thymus Gland* ; Trigeminal Nucleus, Spinal ; Ventromedial Hypothalamic Nucleus

Widespread brain-derived neurotrophic factor (BDNF) mRNA and protein expression has been detected in the brain. Despite substantial overlap between BDNF mRNA and protein expression, there is general anatomical regions, where there is discordance of these expression. We performed, therefore, immunohistochemistry after colchicine treatment into the ventricle to evaluate the possible presence of BDNF-immunoreactive (IR) in the regions where BDNF mRNA was expressed, but not BDNF-IR. The results obtained were as follows; There was substantial increase in the number of BDNF-IR neurons in the anterior olfactory nucleus, the piriform cortex, the cerebral cortex, the claustrum, the stratum pyramidale of the CA2 and the CA3, the granule cell layer of the dentate gyrus, the basolateral amygdaloid nucleus, the lateral geniculate nucleus, the anteromedial thalamic nucleus, the anterodorsal thalamic nucleus, the paraventricular thalamic nucleus, the paraventricular hypothalamic nucleus and the ventromedial hypothalamus nucleus, compared to the same brain area of non-colchicine treated rat. We detected many new BDNF-IR neurons in the stratum pyramidale of the CA1, A1, A2, A4-A10 cell groups, C1-C3 cell groups, the raphe magnus nucleus, the lateral paragigantocellular nucleus and the spinal vestibular nucleus. The results show that the localization of BDNF-IR neurons after colchicine treatment is consistant with that of BDNF mRNA containing neurons in the brain.
Animals ; Anterior Thalamic Nuclei ; Basal Ganglia ; Brain* ; Brain-Derived Neurotrophic Factor ; Cerebral Cortex ; Colchicine* ; Dentate Gyrus ; Hypothalamus ; Immunohistochemistry ; Midline Thalamic Nuclei ; Neurons* ; Paraventricular Hypothalamic Nucleus ; Rats* ; RNA, Messenger