Ablation Of Cortex Research Articles

Intact Performance on Feature-Ambiguous Discriminations in Rats with Lesions of the Perirhinal Cortex

We developed a behavioral paradigm for the rat that made it possible to separate the evaluation of memory functions from the evaluation of perceptual functions. Animals were given extensive training on an automated two-choice discrimination task and then maintained their memory performance at a high level while interpolated probe trials tested visual perceptual ability. The probe trials systematically varied the degree of feature ambiguity between the stimuli, such that perceptual functions could be tested across 14 different levels of difficulty. As feature ambiguity increased, performance declined in an orderly, monotonic manner (from 87% correct to chance, 50% correct). Bilateral lesions of the perirhinal cortex fully spared the capacity to make feature-ambiguous discriminations and the performance of lesioned and intact animals was indistinguishable at every difficulty level. In contrast, the perirhinal lesions did impair recognition memory. The findings suggest that the perirhinal cortex is important for memory and not for perceptual functions.

Post-treatment with amphetamine enhances reinnervation of the ipsilateral side cortex in stroke rats

Amphetamine (AM) treatment has been shown to alter behavioral recovery after ischemia caused by embolism, permanent unilateral occlusion of the common carotid and middle cerebral arteries, or unilateral sensorimotor cortex ablation in rats. However, the behavioral results are inconsistent possibly due to difficulty controlling the size of the lesion before treatment. There is also evidence that AM promotes neuroregeneration in the cortex contralateral to the infarction; however, the effects of AM in the ipsilateral cortex remain unclear. The purpose of this study was to employ T2-weighted imaging (T2WI) to establish controlled criteria for AM treatment and to examine neuroregenerative effects in both cortices after stroke. Adult rats were anesthetized, and the right middle cerebral artery was ligated for 90 min to generate lesions in the ipsilateral cortex. Animals were separated into two equal treatment groups (AM or saline) according to the size of infarction, measured by T2WI at 2 days after stroke. AM or saline was administered to stroke rats every third day starting on day 3 for 4 weeks. AM treatment significantly reduced neurological deficits, as measured by body asymmetry and Bederson's score. T2WI and diffusion tensor imaging (DTI) were used to examine the size of infarction and axonal reinnervation, respectively, before and following treatment on days 2, 10 and 25 after stroke. AM treatment reduced the volume of tissue loss on days 10 and 25. A significant increase in fractional anisotropy ratio was found in the ipsilateral cortex after repeated AM administration, suggesting a possible increase in axonal outgrowth in the lesioned side cortex. Western analysis indicated that AM significantly increased the expression of synaptophysin ipsilaterally and neurofilament bilaterally. AM also enhanced matrix metalloproteinase (MMP) enzymatic activity, determined by MMP zymography in the lesioned side cortex. qRT-PCR was used to examine the expression of trophic factors after the 1st and 2nd doses of AM or saline injection. The expression of BDNF, but not BMP7 or CART, was significantly enhanced by AM in the lesioned side cortex. In conclusion, post-stroke treatment with AM facilitates behavioral recovery, which is associated with an increase in fractional anisotropy activity, enhanced fiber growth in tractography, synaptogenesis, upregulation of BDNF, and MMP activity mainly in the lesioned cortex. Our data suggest that the ipsilateral cortex may be the major target of action in stroke brain after AM treatment.

The Mitochondrial Permeability Transition Pore Regulates Nitric Oxide-Mediated Apoptosis of Neurons Induced by Target Deprivation

Ablation of mouse occipital cortex induces precisely timed and uniform p53-modulated and Bax-dependent apoptosis of thalamocortical projection neurons in the dorsal lateral geniculate nucleus (LGN) by 7 d after lesion. We tested the hypothesis that this neuronal apoptosis is initiated by oxidative stress and the mitochondrial permeability transition pore (mPTP). Preapoptotic LGN neurons accumulate mitochondria, Zn(2+) and Ca(2+), and generate higher levels of reactive oxygen species (ROS), including superoxide, nitric oxide (NO), and peroxynitrite, than LGN neurons with an intact cortical target. Preapoptosis of LGN neurons is associated with increased formation of protein carbonyls, protein nitration, and protein S-nitrosylation. Genetic deletion of nitric oxide synthase 1 (nos1) and inhibition of NOS1 with nitroindazole protected LGN neurons from apoptosis, revealing NO as a mediator. Putative components of the mPTP are expressed in mouse LGN, including the voltage-dependent anion channel (VDAC), adenine nucleotide translocator (ANT), and cyclophilin D (CyPD). Nitration of CyPD and ANT in LGN mitochondria occurs by 2 d after cortical injury. Chemical cross-linking showed that LGN neuron preapoptosis is associated with formation of CyPD and VDAC oligomers, consistent with mPTP formation. Mice without CyPD are rescued from neuron apoptosis as are mice treated with the mPTP inhibitors TRO-19622 (cholest-4-en-3-one oxime) and TAT-Bcl-X(L)-BH4. Manipulation of the mPTP markedly attenuated the early preapoptotic production of reactive oxygen/nitrogen species in target-deprived neurons. Our results demonstrate in adult mouse brain neurons that the mPTP functions to enhance ROS production and the mPTP and NO trigger apoptosis; thus, the mPTP is a target for neuroprotection in vivo.

Corticospinal tract fibers cross the ephrin-B3-negative part of the midline of the spinal cord after brain injury

The fibers of corticospinal tract (CST), which control fine motor function, predominantly project to the contralateral spinal cord, not recross to the ipsilateral side. Ephrin-B3, which is expressed in the midline of the spinal cord, and its receptor, EphA4, are crucial for preventing CST fibers from recrossing the midline in the developing spinal cord. However, these fibers can cross the midline to the denervated side after a unilateral CST or cortical injury. We determined the reason CST fibers can cross the midline after a cortical injury and the changes in ephrin-B3–EphA4 signaling associated with such a crossing. We first examined axonal sprouting from CST fibers after unilateral ablation of the motor cortex in postnatal and adult mice. CST fibers crossed the midline of the spinal cord after cortical ablation, especially when conducted during the early postnatal period. These fibers were well associated with functional recovery after the injury. We next assessed the mRNA expression of ephrin-B3 and EphA4 before and after the ablation. Surprisingly, no changes were detected in the expression patterns. We found, however, that ephrin-B3 expression in the ventral part of the midline disappeared after postnatal day 9 (P9), but was pronounced along the entire midline before P6. Most of the CST fibers crossed the midline through the ventral region, where ephrin-B3 expression was absent. Our results suggest that ephrin-B3 is not expressed along the entire midline of the spinal cord, and sprouting axons can cross the midline at ephrin-B3-negative areas.

Long‐term regulation in calretinin staining in the rat inferior colliculus after unilateral auditory cortical ablation

In this study we analyzed the effects in the inferior colliculus of a unilateral ablation of the auditory cortex in rats. Variations in both calretinin immunoreactivity and protein levels determined by Western blot suggest that such lesions induce changes in the regulation of this calcium-binding protein. Stereological counts of calretinin-immunoreactive neurons in the inferior colliculus 15, 90, and 180 days after the lesion showed a progressive increase in the number of immunoreactive neurons, with a parallel increase in the intensity of staining. Two hundred forty days after the cortical lesion, both the number of immunoreactive neurons and the staining intensity had returned to control values. The effects of the cortical lesion on calretinin regulation are more intense in those inferior colliculus subdivisions more densely innervated by the corticocollicular projection. This finding, along with the time course of calretinin regulation suggests that degeneration of the descending projection is linked to calretinin regulation in the inferior colliculus. We hypothesize, based on the role of calretinin, that the observed increase in immunoreactivity levels seen in the inferior colliculus after lesioning of the auditory cortex may be related to altered excitability in deafferented neurons. Our finding, may reflect adaptive mechanisms to changes in calcium influx and excitability in inferior colliculus neurons induced by lesions of the descending projection from the cortex to the inferior colliculus.

Serum or target deprivation‐induced neuronal death causes oxidative neuronal accumulation of Zn2+ and loss of NAD+

Trophic deprivation-mediated neuronal death is important during development, after acute brain or nerve trauma, and in neurodegeneration. Serum deprivation (SD) approximates trophic deprivation in vitro, and an in vivo model is provided by neuronal death in the mouse dorsal lateral geniculate nucleus (LGNd) after ablation of the visual cortex (VCA). Oxidant-induced intracellular Zn(2+) release ([Zn(2+) ](i) ) from metallothionein-3 (MT-III), mitochondria or 'protein Zn(2+) ', was implicated in trophic deprivation neurotoxicity. We have previously shown that neurotoxicity of extracellular Zn(2+) required entry, increased [Zn(2+) ](i) , and reduction of NAD(+) and ATP levels causing inhibition of glycolysis and cellular metabolism. Exogenous NAD(+) and sirtuin inhibition attenuated Zn(2+) neurotoxicity. Here we show that: (1) Zn(2+) is released intracellularly after oxidant and SD injuries, and that sensitivity to these injuries is proportional to neuronal Zn(2+) content; (2) NAD(+) loss is involved - restoration of NAD(+) using exogenous NAD(+) , pyruvate or nicotinamide attenuated these injuries, and potentiation of NAD(+) loss potentiated injury; (3) neurons from genetically modified mouse strains which reduce intracellular Zn(2+) content (MT-III knockout), reduce NAD(+) catabolism (PARP-1 knockout) or increase expression of an NAD(+) synthetic enzyme (Wld(s) ) each had attenuated SD and oxidant neurotoxicities; (4) sirtuin inhibitors attenuated and sirtuin activators potentiated these neurotoxicities; (5) visual cortex ablation (VCA) induces Zn(2+) staining and death only in ipsilateral LGNd neurons, and a 1 mg/kg Zn(2+) diet attenuated injury; and finally (6) NAD(+) synthesis and levels are involved given that LGNd neuronal death after VCA was dramatically reduced in Wld(s) animals, and by intraperitoneal pyruvate or nicotinamide. Zn(2+) toxicity is involved in serum and trophic deprivation-induced neuronal death.

Natural and lesion-induced apoptosis in the dorsal lateral geniculate nucleus during development

We investigated natural and lesion-induced apoptosis in the developing rat dorsal lateral geniculate nucleus (dLGN). These lesions involved: i) monocular enucleation, and ii) unilateral ablation of the visual cortex at different postnatal ages before eye opening. We identified dying cells as apoptotic with light and electron microscopy, using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and immunohistochemistry for active caspase-3. In the dLGN of normal animals, TUNEL+ cells were detected during the first postnatal week, with a peak at postnatal day (P) 1. Following enucleation at birth or at P7, the frequency of apoptotic cells in the contralateral dLGN increased significantly at postlesion day (PLD) 1 and returned to normal values by PLD7. In contrast to early lesions, enucleation at P14 did not induce significant changes in apoptosis in the dLGN. Cortical lesions performed at P0, P7 or at P14 induced the death of the overwhelming majority of cells in the ipsilateral dLGN, which led to a severe reduction in size of the nucleus by PLD7 and its complete elimination by adulthood. Double labeling with TUNEL and immunofluorescence for neuronal nuclear protein (NeuN) showed that in both normal and lesioned animals, apoptotic cells were mainly neurons. We suggest that: i) apoptosis in the dLGN occurs during the precritical period of neuronal maturation; ii) developing neurons in the dLGN are more dependent on the integrity of their connections with the visual cortex than with the retina for survival; and iii) lesion-induced apoptosis in the dLGN during development depends on the type and extent of the connectivity affected.

A comparison of the effects of days 1 and 10 unilateral lesions of medial prefrontal cortex on cerebral morphogenesis and behavior

The purpose of this study was to compare the behavioral and anatomical effects of unilateral medial prefrontal cortex (mPFC) ablation on newborn (day of birth, P1), neonatal (10 days old, P10), and sham-operated rats. The infant operates were impaired bilaterally at skilled reaching and forelimb inhibition in swimming, and contralaterally at traversing a rung ladder. There was no effect of age-at-injury. They also had mild deficits on spatial navigation tasks. Anatomically, the cortex of the injured hemisphere was generally thinner throughout, with the effect being larger in the rostral half of the hemisphere. In contrast, the medial prefrontal cortex in the intact hemisphere was significantly thicker than in sham controls. There were no effects on cortical thickness elsewhere in the intact hemisphere. Analysis of golgi-stained layer III pyramidal cells in the intact mPFC found the cells to have less extensive dendritic arborization than in the shams. These results contrast with the effect of unilateral motor cortex injuries at the same ages.

Is Top-Down Control from Prefrontal Cortex Necessary for Visual Categorization?

The brain mechanisms underlying visual object categorization remain unclear. In this issue of Neuron, Minamimoto and colleagues introduce a novel task that associates each category with a different incentive value, and they demonstrate that it can be learned within a single session even after ablation of the lateral prefrontal cortex.

Long-term functional recovery in the rat auditory system after unilateral auditory cortex ablation

Conclusions: An intact bilateral auditory corticofugal projection is necessary for the auditory system, and above all its main targets, to start working correctly after an acoustic stimulation. After restricted unilateral cortical lesions, the auditory system is able to recover its function in adult animals at 90 days after surgery. (Post-lesion plasticity in adults.) Objectives: To study the influence of the cortex on the auditory system functionality and to asses its ability for post-lesion recovery. Methods: Restricted unilateral lesions were made in the auditory cortex of adult rats. To evaluate the functionality of the auditory pathway after corticofugal deafferentation, the acoustic startle reflex and prepulse inhibition, together with the auditory brainstem response (ABR), were tested along the survival time. Results: All the three tests showed a decrease in their responses at 15 days post lesion, and a full recovery at 90 days post lesion for the ABR and at 180 days post lesion for the acoustic startle reflex and prepulse inhibition.

Comparative study of the sensitivity of ADC value and T2 relaxation time for early detection of Wallerian degeneration

Background and purpose Wallerian degeneration (WD), the secondary degeneration of axons from cortical and subcortical injuries, is associated with poor neurological outcome. There is some quantitative MR imaging techniques used to estimate the biologic changes secondary to delayed neuronal and axonal losses. Our purpose is to assess the sensitivity of ADC value and T 2 relaxation time for early detection of WD. Methods Ten male Sprague–Dawley rats were used to establish in vivo Wallerian degeneration model of CNS by ipsilateral motor–sensory cortex ablation. 5 days after cortex ablation, multiecho- T 2 relaxometry and multi- b value DWI were acquired by using a 7 T MR imaging scanner. ADC-map and T 2-map were reconstructed by post-processing. ROIs are selected according to pathway of corticospinal tract from cortex, internal capsule, cerebral peduncle, pons, medulla oblongata to upper cervical spinal cord to measure ADC value and T 2 relaxation time of healthy side and affected side. The results were compared between the side with cortical ablation and the side without ablation. Results Excluding ablated cortex, ADC values of the corticospinal tract were significantly increased ( P < 0.05) in affected side compared to the unaffected, healthy side; no difference in T 2 relaxation time was observed between the affected and healthy sides. Imaging findings were correlated with histological examinations. Conclusion As shown in this animal experiment, ADC values could non-invasively demonstrate the secondary degeneration involving descending white matter tracts. ADC values are more sensitive indicators for detection of early WD than T 2 relaxation time.

Transient down-regulation of sound-induced c-Fos protein expression in the inferior colliculus after ablation of the auditory cortex

We tested whether lesions of the excitatory glutamatergic projection from the auditory cortex (AC) to the inferior colliculus (IC) induce plastic changes in neurons of this nucleus. Changes in neuronal activation in the IC deprived unilaterally of the cortico-collicular projection were assessed by quantitative c-Fos immunocytochemistry. Densitometry and stereology measures of sound-induced c-Fos immunoreactivity in the IC showed diminished labeling at 1, 15, 90, and 180 days after lesions to the AC suggesting protein down-regulation, at least up to 15 days post-lesion. Between 15 and 90 days after the lesion, c-Fos labeling recovers, approaching control values at 180 days. Thus, glutamatergic excitation from the cortex maintains sound-induced activity in neurons of the IC. Subdivisions of this nucleus receiving a higher density of cortical innervation such as the dorsal cortex showed greater changes in c-Fos immunoreactivity, suggesting that the anatomical strength of the projection correlates with effect strength. Therefore, after damage of the corticofugal projection, neurons of the IC down-regulate and further recover sound-induced c-Fos protein expression. This may be part of cellular mechanisms aimed at balancing or adapting neuronal responses to altered synaptic inputs.

Analysis of De Novo Cell Cortex Assembly in Blebs as a Novel Assay for Probing Cortical Dynamics and Regulation

The contractile actin cortex drives many cellular processes, such as cell migration and cytokinesis, but little is known about the proteins that regulate its assembly.To address this question, we developed an assay for assessing the involvement of candidate proteins in the recruitment of the main cortical components, actin and myosin, during cortex build-up. One situation where cortex assembly can easily be studied is during the growth of blebs. Blebs are membrane protrusions that are initially devoid of cortical proteins and that subsequently reassemble a cortical layer prior to bleb retraction. They therefore constitute an ideal system for the study of de novo cortex assembly under physiological conditions.In the developed assay, we use laser ablation of the cell cortex to induce bleb growth in a controlled manner and subsequently quantitatively monitor the recruitment of fluorescently labelled actin and myosin during the bleb life cycle. This allows for the extraction of a range of dynamic parameters of cortical assembly that can be compared between control cells and cells with varying levels of candidate proteins. Preliminary data, obtained with this assay, show that proteins typically involved in actin polymerization, such as profilin and cofilin, influence the rates of cortex assembly in HeLa cells. Additionally, the assay allowed us to precisely characterize the dynamics of cortex assembly in control cells, providing new insights into the mechanisms of bleb growth and retraction. From these first tests, we conclude that the developed assay provides a highly sensitive tool for the study of cortex assembly.

Cortical Lesion-Induced Visual Hemineglect Is Prevented by NMDA Antagonist Pretreatment

Large unilateral visual cortex lesions produce enduring contralesional visual orientation deficits. To examine whether glutamate excitotoxicity is involved in establishing these deficits, cats were pretreated with the NMDA receptor antagonist dizocilpine (MK-801) 30 min before unilateral visual cortex ablation. Pretreated MK-801 animals were trained first in an orientation task in which they were required to fixate directly ahead and then orient to stimuli introduced at various eccentricities throughout the visual field. They did not display the characteristic ipsilesional head and neck asymmetries and/or spontaneous ipsiversive rotational behaviors or show the profound contralesional visual neglect seen postoperatively in nonpretreated control animals. Rather, pretreated animals were able to orient to visual stimuli in the contralesional hemifield immediately following surgical recovery. Postmortem histology revealed severe retrograde degeneration of the ipsilesional lateral geniculate nucleus in both experimental groups, suggesting that postlesion visuomotor behavioral competencies in pretreated animals are attributable to preserved function in nongeniculocortical visual pathways. These observations are consistent with the hypothesis that visual cortex lesions normally induce secondary alterations via NMDA-mediated excitotoxicity in these other pathways that prevents them from supporting visuomotor behaviors. The similar behavioral competencies of MK-801-pretreated animals and those whose lesion-induced deficits are ameliorated by removing basal ganglia afferents to the ipsilesional superior colliculus are consistent with this hypothesis and highlight the normal functional capabilities of this circuit. It is likely that MK-801 pretreatment acts, at least in part, by preserving the normal interhemispheric control dynamics with which the basal ganglia influence superior colliculus-mediated orientation behaviors.

N-methyl- d-aspartate receptors in the insular cortex modulate baroreflex in unanesthetized rats

In the present study, we report the effect of insular cortex (IC) ablation caused by bilateral microinjection of the non-selective synaptic blocker CoCl 2 on cardiac baroreflex response in unanesthetized rats as well as the involvement of local glutamatergic neurotransmission. Unilateral (left or right) microinjection of CoCl 2 (1 nmol/ 100 nL) did not affect the bradycardiac response to blood pressure increase evoked by intravenous infusion of phenylephrine nor the tachycardiac response to blood pressure decrease caused by intravenous infusion of sodium nitroprusside, 10 min after CoCl 2. Bilateral microinjection of CoCl 2 into IC decreased the magnitude of reflex bradycardia without affecting tachycardiac responses. Baroreflex activity returned to control values 60 min after CoCl 2 microinjection, confirming its reversible effect. Further we studied the possible involvement of IC-glutamatergic neurotransmission in baroreflex modulation. We observed that bilateral microinjection of the selective NMDA receptor antagonist LY235959 (4 nmol/100 nL) into the IC decreased the magnitude of reflex bradycardia without affecting tachycardiac responses. IC treatment with the selective non-NMDA antagonist NBQX (4 nmol/100 nL) did not affect baroreflex activity. The results suggest that synapses within the IC have a tonic excitatory influence on the baroreflex parasympathetic component. Moreover, the present data suggest that local NMDA-receptors are involved in the IC-mediated tonic excitatory influence on baroreflex parasympathetic activity.

Long-term functional recovery in the rat auditory system after unilateral auditory cortex ablation

An intact bilateral auditory corticofugal projection is necessary for the auditory system, and above all its main targets, to start working correctly after an acoustic stimulation. After restricted unilateral cortical lesions, the auditory system is able to recover its function in adult animals at 90 days after surgery. (Post-lesion plasticity in adults.) To study the influence of the cortex on the auditory system functionality and to asses its ability for post-lesion recovery. Restricted unilateral lesions were made in the auditory cortex of adult rats. To evaluate the functionality of the auditory pathway after corticofugal deafferentation, the acoustic startle reflex and prepulse inhibition, together with the auditory brainstem response (ABR), were tested along the survival time. All the three tests showed a decrease in their responses at 15 days post lesion, and a full recovery at 90 days post lesion for the ABR and at 180 days post lesion for the acoustic startle reflex and prepulse inhibition.

Deleterious effects of minocycline after in vivo target deprivation of thalamocortical neurons in the immature, metallothionein‐deficient mouse brain

Compared with adults, immature metallothionein I and II knockout (MT(-/-)) mice incur greater neuronal loss and a more rapid rate of microglia accumulation after target deprivation-induced injury. Because minocycline has been proposed to inhibit microglial activation and associated production of neuroinflammatory factors, we investigated its ability to promote neuronal survival in the immature, metallothionein-deficient brain. After ablation of the visual cortex, 10-day-old MT(-/-) mice were treated with minocycline or saline and killed 24 or 48 hr after injury. By means of stereological methods, the number of microglia and neurons were estimated in the ipsilateral dorsal lateral geniculate nucleus (dLGN) by an investigator blinded to the treatment. No effect on neuronal survival was observed at 24 hr, but 48 hr after injury, an unanticipated but significant minocycline-mediated increase in neuronal loss was detected. Further, while failing to inhibit microglial accumulation, minocycline treatment increased the proportion of amoeboid microglia in the ipsilateral dLGN. To understand the molecular mechanisms underlying this neurotoxic response, we identified minocycline-mediated changes in the expression of three potentially proapoptotic/inflammatory genes: growth arrest- and DNA damage-inducible gene 45gamma (GADD45gamma); interferon-inducible protein 1 (IFI1), and cytokine-induced growth factor. We also observed increased mitogen-activated protein kinase p38 phosphorylation with minocycline treatment. Although minocycline inhibited calpain activity at 12 hr after injury, this effect was not sustained at 24 hr. Together, these results help to explain how minocycline has a deleterious effect on neuronal survival in this injury model.

Motor cortex stroke impairs individual digit movement in skilled reaching by the rat

Over 30 years ago, Castro [(1972) Brain Res., 37, 173-185] proposed that motor cortex (MtCx) ablation produced deficits in digital usage that contributed to the rat's impairments in a reach-to-eat task, but the impairment was not directly documented. The present study examined digit use in control rats and rats with MtCx lesions using high-speed (1000 f/s) video recording. Temporal and spatial characteristics of individual digits were evaluated by digitizing the tip of the digits and digital joints using the motion measurement system Peak Motus. Control rats displayed differential digital use during grasping actions and MtCx damage reduced individual digit movement, both as the paw was pre-shaped for grasping and in the grasping action itself. The findings show that although grasping is retained following MtCx damage, MtCx is essential for dexterous movement. The results are discussed in relation to the idea that rodent MtCx is not only necessary for rotatory movements of the limb, but also for digital control and in relation to the similarities of rodent digit use to that described for primates.

Erythropoietin improves spatial delayed alternation in a T-maze in rats subjected to ablation of the prefrontal cortex

Systemically administered human recombinant erythropoietin (EPO) may have the potential to reduce the cognitive and behavioural symptoms of mechanical brain injury. In a series of studies we address this possibility. Previously, we studied the effects of EPO given to fimbria-fornix transected rats at the moment of injury. We have found that such treatment improves substantially the posttraumatic acquisition of allocentric place learning tasks administered in a water maze and in an 8-arm radial maze as well as a spatial delayed alternation task administered in a T-maze. It is, however, essential also to evaluate this clinically important ability of EPO after other types of mechanical brain injury. Consequently, we presently studied the effects of similarly administered EPO in rats subjected to bilateral subpial aspiration of the anteromedial prefrontal cortex as well as control operated rats, respectively. We evaluated the posttraumatic behavioural/cognitive abilities of these animals in a spatial delayed alternation task performed in a T-maze. Administration of EPO to the prefrontally ablated rats was associated with a reduction of the lesion-associated behavioural impairment—while such an impairment was clearly seen in the saline injected prefrontally ablated group. In sham operated rats administration of EPO did not influence the task acquisition significantly. The results of the present study confirm our previous demonstrations that EPO is able to reduce the behavioural/cognitive consequences of mechanical brain injury. This ability is emphasized by its relative independence on the type of lesion as well as the neural structure affected.

Successful radiofrequency ablation of the cerebral cortex in pigs using the venous system: Possible implications for treating CNS disorders

When pharmacotherapy for epilepsy fails, surgical options, although efficacious, are highly invasive. We explored whether ablation of the cerebral cortex can be performed utilizing the cerebral venous system. Mapping and radiofrequency ablation was performed via the venous system in two pigs. Eight targeted sites were successfully accessed and four targeted sites successfully ablated via the central cerebral venous network. Electrophysiological mapping and radiofrequency ablation of the cerebral cortex can be performed via the cerebral veins.