Ipsilateral Thalamus Research Articles

Quantification of pain-induced changes in cerebral blood flow by perfusion MRI

The purpose of this study was to assess if the functional activation caused by painful stimuli could be detected with arterial spin labeling (ASL), which is a non-invasive magnetic resonance imaging (MRI) technique for measuring cerebral blood flow (CBF). Because ASL directly measures blood flow, it is well suited to pain conditions that are difficult to assess with current functional MRI, such as chronic pain. However, the use of ASL in neuroimaging has been hampered by its low sensitivity. Recent improvements in MRI technology, namely increased magnetic field strengths and phased array receiver coils, should enable ASL to measure the small changes in CBF associated with pain. In this study, healthy volunteers underwent two ASL imaging sessions, during which a painful thermal stimulus was applied to the left hand. The results demonstrated that the ASL technique measured changes in regional CBF in brain regions that have been previously identified with pain perception. These included bilateral CBF changes in the insula, secondary somatosensory, and cingulate cortices, as well as the supplementary motor area (SMA). Also observed were contralateral primary somatosensory and ipsilateral thalamic CBF changes. The average change in CBF for all regions of interest was 3.68 ml/100 g/min, ranging from 2.97 ml/100 g/min in ipsilateral thalamus to 4.91 ml/100 g/min in contralateral insula. The average resting global CBF was 54 ± 9.7 ml/100 g/min, and there was no change in global CBF due to the noxious thermal stimulus.

Histopathologic and neurobehavioral evaluation of a standardized fluid percussion model of brain trauma in the rat

For 5 male Sprague Dawley rats/group: Group 1 had a craniotomy; Group 2 had a craniotomy with a temporary luer lock fitting applied; and Group 3 additionally had a fluid percussive injury of approximately 5.5 atmospheres through the temporary luer lock to the exposed right lateral cerebral cortex. The skull defect was closed and behavioral assessments were performed at 2 hours after recovery from anesthesia, and again on Days 1, 3 and 14 post insult. The group given fluid percussion had deficits on balance beam, catalepsy and startle responses on day 0 that resolved at later timepoints. After 2 weeks, rats were euthanized under anesthesia and their brains were perfused in situ. Brains were trimmed at 2 mm intervals. Tissue loss at the cerebral cortical surface was estimated from H&E-stained sections using an ocular grid and averaged 2.3,1.9, and 6.1 mm2 respectively. In addition to greater loss of cerebral cortical tissue, the fluid percussion group had focal gliosis in the white matter, and focal neuronal degeneration visible with Fluoro Jade B staining in the deep cortex ventral and lateral to the site, as well as increased GFAP staining in the ipsilateral dorsal thalamus. Perl's stain showed traces of iron consistent with previous hemorrhage at the site in all groups and in the deeper areas of gliosis in Group 3.

(659): Using perfusion MRI to measure pain-induced changes in cerebral blood flow

Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) technique for measuring cerebral blood flow (CBF). Because ASL directly measures blood flow, it is well suited to pain conditions that are difficult to assess with current functional MRI, such as chronic pain. However, the use of ASL in neuroimaging has been hampered by its low sensitivity. Recent improvements in MRI technology, namely increased magnetic field strengths and phased array receiver coils, should enable ASL to measure the small changes in CBF associated with pain. The purpose of this study was to assess whether the functional activation caused by acute painful stimuli could be detected with an ASL technique. Fourteen healthy volunteers underwent two 11-minute ASL imaging sessions, during which a painful thermal stimulus (mean = 48.9 °C) was applied to the left hand. Functional image analysis software (SPM2) was used for both the fixed effects individual analyses and the random effects group analysis. The results demonstrated that the ASL technique measured changes in regional CBF in brain regions that have been previously identified with pain processing. These included bilateral CBF changes in the insula, secondary somatosensory, and cingulate cortices, as well as the supplementary motor area (SMA). Also observed were contralateral primary somatosensory and ipsilateral thalamic CBF changes. The average change in CBF for all regions of interest was 3.68 ml/100g/min, ranging from 2.97 ml/100g/min in ipsilateral thalamus to 4.91 ml/100g/min in contralateral insula. Although both sessions of data were used to obtain these results, the analysis revealed that data from a single 11-minute session were sufficient to map the pain-related areas of the brain. With its improved sensitivity, ASL will allow for more comprehensive studies of chronic pain conditions, and prolonged pain stimuli, such as tonic pain, particularly with regards to their associated cognitive and emotional components.

Hippocampal volumes and diffusion-weighted image findings in children with prolonged febrile seizures

To assess hippocampal volumes (HV) and signal changes on diffusion-weighted imaging (DWI) within 5 days of prolonged febrile seizures (PFS) and compare them with the PFS duration and EEG. We studied 12 children (mean age: 32 +/- 21 months, range 10 months-5 years) within 5 days of a first episode of PFS (a seizure or series of seizures lasting for 30 min or longer, without return of consciousness between the seizures). The HV measurements were carried out using high-resolution magnetic resonance imaging and signal intensity abnormalities were evaluated visually on DWI. HV in patients were compared with those of 13 neurologically normal controls (mean age 31 +/- 16 months, range 15 months-5 years). HV abnormalities correlated with PFS duration. HV and DWI abnormalities were compared with EEG abnormalities. Seizure duration ranged from 40 to 95 min. In seven out of twelve patients, seizures were refractory and lasted for 60 min or longer despite intravenous infusion of diazepam. In the patients with PFS for 60 min or longer, HV were significantly larger than that of controls. In all patients, there was a positive correlation between HV and seizure duration. DWI showed hyperintensity in unilateral hippocampus in three patients with intractable seizures, ipsilateral thalamus in two, and cingulate in one. EEG showed abnormalities in temporal areas ipsilateral to the DWI abnormalities in these patients. Large HV and hippocampal hyperintensity on DWI were seen in patients with refractory PFS. Our results suggest that medically refractory PFS lasting for 60 min or longer may cause structural changes in limbic structures that could promote later epileptogenesis.

Reduced Functional Deficits, Neuroinflammation, and Secondary Tissue Damage after Treatment of Stroke by Nonerythropoietic Erythropoietin Derivatives

Carbamylerythropoietin (CEPO) does not bind to the classical erythropoietin (EPO) receptor. Nevertheless, similarly to EPO, CEPO promotes neuroprotection on the histologic level in short-term stroke models. In the present study, we investigated whether CEPO and other nonerythropoietic EPO analogs could enhance functional recovery and promote long-term histologic protection after experimental focal cerebral ischemia. Rats were treated with the compounds after focal cerebral ischemia. Animals survived 1, 7, or 60 days and underwent behavioral testing (sensorimotor and foot-fault tests). Brain sections were stained and analyzed for Iba-1, myeloperoxidase, Tau-1, CD68 (ED1), glial fibrillary acidic protein (GFAP), Fluoro-Jade B staining, and overall infarct volumes. Treatment with CEPO reduced perifocal microglial activation (P<0.05), polymorphomonuclear cell infiltration (P<0.05), and white matter damage (P<0.01) at 1 day after occlusion. Carbamylerythropoietin-treated rats showed better functional recovery relative to vehicle-treated animals as assessed 1, 7, 14, 28, and 50 days after stroke. Both GFAP and CD68 were decreased within the ipsilateral thalamus of CEPO-treated animals 60 days postoperatively (P<0.01 and P<0.05, respectively). Furthermore, behavioral analysis showed efficacy of CEPO treatment even if administered 24 h after the stroke. Other nonerythropoietic derivatives such as carbamylated darbepoetin alfa and the mutant EPO-S100E were also found to protect against ischemic damage and to improve postischemic neurologic function. In conclusion, these results show that postischemic intravenous treatment with nonerythropoietic EPO derivatives leads to improved functional recovery, which may be linked to their long-term effects against neuroinflammation and secondary tissue damage.

Diabetic Goto-Kakizaki rats display pronounced hyperglycemia and longer-lasting cognitive impairments following ischemia induced by cortical compression

Hyperglycemia has been shown to worsen the outcome of brain ischemia in several animal models but few experimental studies have investigated impairments in cognition induced by ischemic brain lesions in hyperglycemic animals. The Goto-Kakizaki (GK) rat naturally develops type 2 diabetes characterized by mild hyperglycemia and insulin resistance. We hypothesized that GK rats would display more severe cerebral damage due to hyperglycemia-aggravated brain injury and, accordingly, more severe cognitive impairments. In this study, recovery of motor and cognitive functions of GK and healthy Wistar rats was examined following extradural compression (EC) of the sensorimotor cortex. For this purpose, tests of vestibulomotor function (beam-walking) and combined tests of motor function and learning (locomotor activity from day (D) 1 to D5, operant lever-pressing from D14 to D25) were used. EC consistently reduced cerebral blood flow in both strains. Anesthesia-challenge and EC resulted in pronounced hyperglycemia in GK but not in Wistar rats. Lower beam-walking scores, increased locomotor activity, impairments in long-term habituation and learning of operant lever-pressing were more pronounced and observed at later time-points in GK rats. Fluoro-Jade, a marker of irreversible neuronal degeneration, revealed consistent degeneration in the ipsilateral cortex, hippocampus and thalamus at 2, 7 and 14 days post-compression. The amount of degeneration in these structures was considerably higher in GK rats. Thus, GK rats exhibited marked hyperglycemia during EC, as well as longer-lasting behavioral deficits and increased neurodegeneration during recovery. The GK rat is thus an attractive model for neuropathologic and cognitive studies after ischemic brain injury in hyperglycemic rats.

Changes in neuronal connectivity after stroke in rats as studied by serial manganese-enhanced MRI

Loss of function and subsequent spontaneous recovery after stroke have been associated with physiological and anatomical alterations in neuronal networks in the brain. However, the spatiotemporal pattern of such changes has been incompletely characterized. Manganese-enhanced MRI (MEMRI) provides a unique tool for in vivo investigation of neuronal connectivity. In this study, we measured manganese-induced changes in longitudinal relaxation rate, R(1), to assess the spatiotemporal pattern of manganese distribution after focal injection into the intact sensorimotor cortex in control rats (n=10), and in rats at 2 weeks after 90-min unilateral occlusion of the middle cerebral artery (n=10). MEMRI data were compared with results from conventional tract tracing with wheat-germ agglutinin horseradish peroxidase (WGA-HRP). Distinct areas of the sensorimotor pathway were clearly visualized with MEMRI. At 2 weeks after stroke, manganese-induced changes in R(1) were significantly delayed and diminished in the ipsilateral caudate putamen, thalamus and substantia nigra. Loss of connectivity between areas of the sensorimotor network was also identified from reduced WGA-HRP staining in these areas on post-mortem brain sections. This study demonstrates that MEMRI enables in vivo assessment of spatiotemporal alterations in neuronal connectivity after stroke, which may lead to improved insights in mechanisms underlying functional loss and recovery after stroke.

Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti‐myelin‐associated glycoprotein antibody

Axonal injury is a hallmark of traumatic brain injury (TBI) and is associated with a poor clinical outcome. Following central nervous system injury, axons regenerate poorly, in part due to the presence of molecules associated with myelin that inhibit axonal outgrowth, including myelin-associated glycoprotein (MAG). The involvement of MAG in neurobehavioral deficits and tissue loss following experimental TBI remains unexplored and was evaluated in the current study using an MAG-specific monoclonal antibody (mAb). Anesthetized rats (n=102) were subjected to either lateral fluid percussion brain injury (n=59) or sham injury (n=43). In surviving animals, beginning at 1 h post-injury, 8.64 microg anti-MAG mAb (n=33 injured, n=21 sham) or control IgG (n=26 injured, n=22 sham) was infused intracerebroventricularly for 72 h. One group of these rats (n=14 sham, n=11 injured) was killed at 72 h post-injury for verification of drug diffusion and MAG immunohistochemistry. All other animals were evaluated up to 8 weeks post-injury using tests for neurologic motor, sensory and cognitive function. Hemispheric tissue loss was also evaluated at 8 weeks post-injury. At 72 h post-injury, increased immunoreactivity for MAG was seen in the ipsilateral cortex, thalamus and hippocampus of brain-injured animals, and anti-MAG mAb was detectable in the hippocampus, fimbria and ventricles. Brain-injured animals receiving anti-MAG mAb showed significantly improved recovery of sensorimotor function at 6 and 8 weeks (P<0.01) post-injury when compared with brain-injured IgG-treated animals. Additionally, at 8 weeks post-injury, the anti-MAG mAb-treated brain-injured animals demonstrated significantly improved cognitive function and reduced hemispheric tissue loss (P<0.05) when compared with their brain-injured controls. These results indicate that MAG may contribute to the pathophysiology of experimental TBI and treatment strategies that target MAG may be suitable for further evaluation.

Effect of corpus callosum damage on ipsilateral motor activation in patients with multiple sclerosis: A functional and anatomical study

Functional MRI (fMRI) studies have shown increased activation of ipsilateral motor areas during hand movement in patients with multiple sclerosis (MS). We hypothesized that these changes could be due to disruption of transcallosal inhibitory pathways. We studied 18 patients with relapsing-remitting MS. Conventional T1- and T2-weighted images were acquired and lesion load (LL) measured. Diffusion tensor imaging (DTI) was performed to estimate fractional anisotropy (FA) and mean diffusivity (MD) in the body of the corpus callosum (CC). fMRI was obtained during a right-hand motor task. Patients were studied to evaluate transcallosal inhibition (TCI, latency and duration) and central conduction time (CCT). Eighteen normal subjects were studied with the same techniques. Patients showed increased MD (P < 0.0005) and reduced FA (P < 0.0005) in the body of the CC. Mean latency and duration of TCI were altered in 12 patients and absent in the others. Between-group analysis showed greater activation in patients in bilateral premotor, primary motor (M1), and middle cingulate cortices and in the ipsilateral supplementary motor area, insula, and thalamus. A multivariate analysis between activation patterns, structural MRI, and neurophysiological findings demonstrated positive correlations between T1-LL, MD in the body of CC, and activation of the ipsilateral motor cortex (iM1) in patients. Duration of TCI was negatively correlated with activation in the iM1. Our data suggest that functional changes in iM1 in patients with MS during a motor task partially represents a consequence of loss of transcallosal inhibitory fibers.

Functional magnetic resonance imaging in rodents: Methodology and application to spinal cord injury

Functional MRI (fMRI) on spinal cord-injured rodents at 4 and 8 weeks post injury (PI) is described. The paradigm for fMRI, based on electrical stimulation of rat paws, was automated using an in-house designed microprocessor-based controller that was interfaced to a stimulator. The MR images were spatially normalized to the Paxinos and Watson atlas using publicly available digital images of the cryosections. In normal uninjured animals, the activation was confined to the contralateral somatosensory cortex. In contrast, in injured animals, extensive activation, which included structures such as ipsilateral cortex, thalamus, hippocampus, and the caudate putamen, was observed at 4 and 8 weeks PI. Quantitative cluster analysis was carried out to calculate the volumes and centers of activation in individual brain structures. Based on this analysis, significant increase in activation between 4 and 8 weeks was observed only in the ipsilateral caudate putamen and thalamus. These studies suggest extensive and ongoing brain reorganization in spinal cord-injured animals.

Short-term facilitation in the anterior cingulate cortex following stimulation of the medial thalamus in the rat

The present study examined the distribution and localization of synaptic activities (field potentials, multiunit activities and sink source currents) evoked in the anterior cingulate cortex (ACC) by electrical paired pulse stimulation of the ipsilateral medial thalamus (MT). Male Sprague–Dawley rats were anesthetized with halothane (1.0–1.5%), and electrical paired pulses stimuli (100–300 μA, inter-pulse interval, 100 ms) were delivered to the MT. Tungsten microelectrodes and a multichannel Michigan probe were used to record the evoked field potentials and multiunit activities in the ACC. Paired pulse stimulation facilitated field potentials and multiunit activities elicited from several MT nuclei. The second component of the negative field potential (com2) was augmented to about 2.5 times that of the first component (com1), and the integrated multiunit activities were facilitated by about 1.6-fold. Paired stimulation produced an expansion of the maximal negative potential from layer II/III into the deeper layers of the cingulate cortex area 1 (Cg1). Furthermore, the potentiated activity spread into adjacent secondary motor cortex (M2) and prelimbic cortex (PrL). Meanwhile, the area covered by the maximal integrated multiunit activities expanded from layer V (com1) to layers II–V (com2) in M2, Cg1 and PrL. The current source density (CSD) analysis revealed that the short latency sinks were located in layer II/III and layer V/VI. The sink currents were potentiated and expanded to more superficial and to deeper layers when a second pulse was delivered with a 100-ms time delay. Sink currents and the paired pulse facilitation (PPF) were reduced by morphine treatment (5 mg/kg, i.v.), and this effect could be blocked by naloxone. Electrical stimulation at 10 Hz in the MT induced more pronounced c-fos immunolabeling of neurons in the medial prefrontal cortex than did 1-Hz stimulation. The short-term facilitation occurred in the middle layers and expanded to the deeper layers of the ACC. These changes may mediate the effective signal transference in the specific frequency associated with painful responses.

Increased thalamic neurodegeneration following ischaemic cortical stroke in osteopontin-deficient mice

Inflammation aggravates brain injury caused by stroke and neurodegeneration. Osteopontin (OPN) is a cytokine-like glycoprotein that binds to various integrins and CD44 variants. OPN exerts proinflammatory effects in autoimmune conditions but also has cytoprotective properties and participates in wound healing. In this study, we addressed the role of OPN in ischaemic brain injury using OPN knock-out (KO) mice in models of cortical stroke. Compared with wild-type animals, OPN KO mice exhibited unaltered infarct development at the primary injury site but greatly increased retrograde degeneration of the ipsilateral thalamus. Thalamic neurodegeneration in OPN-deficient mice was associated with pronounced microglia activation and inflammatory gene expression and could be attenuated via pharmacological blockade of the inducible nitric oxide synthase (iNOS). Therefore, delayed neurodegeneration in OPN-deficient mice was at least partly due to an excessive release of nitric oxide via the iNOS pathway. Neuroprotective and anti-inflammatory effects of OPN may be relevant for a variety of neurological disease conditions.

Parkinson Disease: Pattern of Functional MR Imaging Activation during Deep Brain Stimulation of Subthalamic Nucleus—Initial Experience

To prospectively determine the pattern of functional magnetic resonance (MR) imaging activation at 3 T produced by deep brain stimulation (DBS) of subthalamic nucleus (STN) for treatment of Parkinson disease and to determine the safety of DBS electrode stimulation during functional MR imaging at 3 T. Informed consent was obtained from all subjects participating in the study, and the study protocol was approved by the institutional review board at the Cleveland Clinic Foundation and was HIPAA compliant. After extensive phantom safety testing of DBS lead systems, five patients (three men, two women; mean age, 49.4 years +/- 14.5 [standard deviation]; range, 31-74 years) with percutaneously extended bilateral DBS electrodes placed in the STN for treatment of Parkinson disease were examined at 3 T on the 1st or 2nd postoperative day. Imaging consisted of a three-dimensional anatomic data set with leads disconnected and a blood oxygen level-dependent functional MR image with a single lead connected to the external pulse generator in the MR imaging control room by using stimulation parameters previously determined to produce optimal stimulation for alleviation of symptoms. A total of nine leads were tested with the functional MR imaging protocol. Subjects underwent neurologic examination immediately before and after MR imaging. All five patients completed the study without change in their neurologic examination and with activation seen in eight of nine electrodes stimulated. Activation was seen in the ipsilateral basal ganglia in all subjects and ipsilateral thalamus in six of the electrodes tested. Two of the electrode stimulations demonstrated additional activation in the STN and/or substantia nigra region adjacent to the electrode tip. For three electrode stimulations, activation was seen in the contralateral superior cerebellum. Therapeutically effective DBS of STN can be performed safely during functional MR imaging at 3 T and produces a consistent pattern of ipsilateral activation of deep brain motor structures.

Hypothalamic Deep Brain Stimulation in Positron Emission Tomography

Recently, functional imaging data have underscored the crucial role the hypothalamus plays in cluster headache, one of the most severe forms of primary headache. This prompted the application of hypothalamic deep brain stimulation. Yet, it is not apparent how stimulation of an area that is thought to act as a pace-maker for acute headache attacks is able to prevent these attacks from occurring. We addressed this issue by examining 10 operated chronic cluster headache patients, using H2(15O)-positron emission tomography and alternately switching the hypothalamic stimulator on and off. The stimulation induced activation in the ipsilateral hypothalamic gray (the site of the stimulator tip), the ipsilateral thalamus, somatosensory cortex and praecuneus, the anterior cingulate cortex, and the ipsilateral trigeminal nucleus and ganglion. We additionally observed deactivation in the middle temporal gyrus, posterior cingulate cortex, and contralateral anterior insula. Both activation and deactivation are situated in cerebral structures belonging to neuronal circuits usually activated in pain transmission and notably in acute cluster headache attacks. Our data argue against an unspecific antinociceptive effect or pure inhibition of hypothalamic activity. Instead, the data suggest a hitherto unrecognized functional modulation of the pain processing network as the mode of action of hypothalamic deep brain stimulation in cluster headache.

Neurons in the dorsal column nuclei of the rat emit a moderate projection to the ipsilateral ventrobasal thalamus

The dorsal column nuclei (DCN; gracile and cuneate nuclei) give rise to the medial lemniscus, the fibre system that provides an organised somatosensory input to the thalamus. Unlike the spinothalamic and trigeminothalamic tracts that project, also to the ipsilateral thalamus, the medial lemniscus system is believed to be entirely crossed. We demonstrate that DCN emit a small number of axons that reach the ipsilateral thalamus. As retrograde fluorescent neuronal tracer Fluoro-gold was stereotaxically injected in the ventrobasal thalamus of nine young adult Wistar rats. The injection foci were voluminous and encroached upon adjacent nuclei, but the periphery of the injection halo never spilled over to the contralateral thalamus. All sections of the contralateral gracile and cuneate nuclei and the midline nucleus of Bischoff contained abundant retrogradely labelled neurons. The comparison with the Nissl-stained parallel sections suggests that approximately 70-80% of the DCN neurons project to the contralateral thalamus. Counting of retrogradely labelled neurons in two cases revealed 4,809 and 4,222 neurons in the contralateral and 265 and 214 in the ipsilateral DCN, respectively. Thus, although less prominent than the ipsilateral spinothalamic tract, the lemniscal system also emits an ipsilateral projection that accounts for about 5% of the neuronal population in DCN that innervates the ventrobasal thalamus.

Osteopontin mediates neuroprotection via inhibition of inducible nitric oxide synthase

Neurodegeneration following ischemic stroke extends from the ischemic infarct to nonischemic subcortical regions such as the ipsilateral thalamus. At both sites, inflammation with activation of resident microglia/brain macrophage ensues and may exacerbate the degenerative process. Osteopontin (OPN) is a macrophage-derived secreted glycoprotein with cytokine-like and chemoattractant properties mediated via RGD-binding integrin receptors and CD44. OPN exerts proinflammatory effects in autoimmune conditions, but also participates in beneficial wound healing responses. Here, we addressed the role of OPN in ischemic brain injury using OPN knock-out (KO) mice in models of cortical stroke. Compared to wild-type (WT) animals, OPN KO mice exhibited unaltered infarct development at the primary injury site but greatly increased secondary neurodegeneration of the ipsilateral thalamus. Thalamic neurodegeneration in OPN-deficient mice was associated with excessive microglia activation and inflammatory gene expression and could be attenuated via pharmacologic blockade of the inducible nitric oxide synthase (iNOS). Thus, OPN provided neuroprotection through down-regulation of microglia activation and iNOS. OPN-dependent pathways may represent a new target of neuroprotective therapy in neurodegenerative diseases and stroke.

Regional energetic dysfunction in hippocampal epilepsy

There is increasing evidence for a dysfunctional metabolic network in human mesial temporal lobe epilepsy (MTLE). To further describe this, we evaluated the bioenergetic status in unilateral MTLE inter-regionally and in relation to neuropathology. We used whole brain high field (4 T) 31P MR spectroscopic imaging to determine in vivo PCr and ATP, studying n=22 patients (all candidates for hippocampal resection) and n=14 control volunteers. The degree of bioenergetic impairment was assessed by calculating the ratio of PCr to ATP. Compared to controls, patients demonstrated significant decreases in PCr/ATP from the ipsilateral amygdala and pes (0.84 +/- 0.14, 0.87 +/- 0.10, respectively, patients vs 0.97 +/- 0.15, 0.98 +/- 0.16, controls). In patients, the ipsilateral thalamic energetics positively correlated with contralateral hippocampal energetics. In addition, the ipsilateral thalamic and striatal energetics negatively correlated with hippocampal total glial counts. These data are consistent with a view that in MTLE, the bilateral hippocampi, ipsilateral thalamus and striatum are linked in their energetic depression, possibly reflecting the propagation of seizures throughout the brain.

Selective GABAergic Control of Higher-Order Thalamic Relays

GABAergic signaling is central to the function of the thalamus and has been traditionally attributed primarily to the nucleus reticularis thalami (nRT). Here we present a GABAergic pathway, distinct from the nRT, that exerts a powerful inhibitory effect selectively in higher-order thalamic relays of the rat. Axons originating in the anterior pretectal nucleus (APT) innervated the proximal dendrites of relay cells via large GABAergic terminals with multiple release sites. Stimulation of the APT in an in vitro slice preparation revealed a GABA(A) receptor-mediated, monosynaptic IPSC in relay cells. Activation of presumed single APT fibers induced rebound burst firing in relay cells. Different APT neurons recorded in vivo displayed fast bursting, tonic, or rhythmic firing. Our data suggest that selective extrareticular GABAergic control of relay cell activity will result in effective, state-dependent gating of thalamocortical information transfer in higher-order but not in first-order relays.

MicroPET detection of enhanced 18F-FDG utilization by PKA inhibitor in awake rat brain

To obtain PET imaging of glucose metabolism in the brains of conscious rats, a method of rat head fixation was developed. PET measurement with microPET was performed for 60 min after 18F-FDG injection. Significant enhancement of glucose utilization in the right striatum was observed with infusion of Rp-adenosine-3,5-cyclic phosphorothioate triethylamine (Rp-cAMPS). FDG uptake increments were also seen in the ipsilateral frontal cortex and thalamus. As initial FDG uptake in the brain was not significantly altered by Rp-cAMPS, increased glucose metabolism might be due to an increase in the phosphorylation rate by hexokinase rather than the delivery process from plasma to the brain. In contrast to awake rats, the effect of Rp-cAMPS was abolished by anesthesia using chloral hydrate, indicating that neuronal activity has an important role in short term regulation of hexokinase activity through the cAMP/PKA system in the brain. These results strongly demonstrated the value of measuring glucose utilization in the brains of conscious rats.

Longitudinal thalamic diffusion changes after middle cerebral artery infarcts

Background: Cerebral infarcts are responsible for functional alterations and microscopic tissue damage at distance from the ischaemic area. Such remote effects have been involved in stroke recovery. Thalamic hypometabolism is...