Degeneration of axotomized projection neurons in the rat dLGN: temporal progression of events and their mitigation by a single administration of FGF2.

Removal of visual cortex in the rat axotomizes projection neurons in the dorsal lateral geniculate nucleus (dLGN), leading to cytological and structural changes and apoptosis. Biotinylated dextran amine was injected into the visual cortex to label dLGN projection neurons retrogradely prior to removing the cortex in order to quantify the changes in the dendritic morphology of these neurons that precede cell death. At 12 hours after axotomy we observed a loss of appendages and the formation of varicosities in the dendrites of projection neurons. During the next 7 days, the total number of dendrites and the cross-sectional areas of the dendritic arbors of projection neurons declined to about 40% and 20% of normal, respectively. The response of dLGN projection neurons to axotomy was asynchronous, but the sequence of structural changes in individual neurons was similar; namely, disruption of dendrites began within hours followed by cell soma atrophy and nuclear condensation that commenced after the loss of secondary dendrites had occurred. However, a single administration of fibroblast growth factor-2 (FGF2), which mitigates injury-induced neuronal cell death in the dLGN when given at the time of axotomy, markedly reduced the dendritic degeneration of projection neurons. At 3 and 7 days after axotomy the number of surviving dendrites of dLGN projection neurons in FGF-2 treated rats was approximately 50% greater than in untreated rats, and the cross-sectional areas of dendritic arbors were approximately 60% and 50% larger. Caspase-3 activity in axotomized dLGN projection neurons was determined by immunostaining for fractin (fractin-IR), an actin cleavage product produced exclusively by activated caspase-3. Fractin-IR was seen in some dLGN projection neurons at 36 hours survival, and it increased slightly by 3 days. A marked increase in reactivity was seen by 7 days, with the entire dLGN filled with dense fractin-IR in neuronal cell somas and dendrites.

An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys: in vivo positron emission tomography imaging of glial activation.

We examined lateral geniculate nucleus (LGN) degeneration as an indicator for possible diagnosis of glaucoma in experimental glaucoma monkeys using positron emission tomography (PET). Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty in the left eyes of 5 cynomolgus monkeys. Glial cell activation was detected by PET imaging with [(11)C]PK11195, a PET ligand for peripheral-type benzodiazepine receptor (PBR), before and at 4 weeks after laser treatment (moderate glaucoma stage). At mild, moderate, and advanced experimental glaucoma stages (classified by histological changes based on the extent of axonal loss), brains were stained with cresyl violet, or antibodies against PBR, Iba-1 (a microglial marker), and GFAP (an activated astrocyte marker). In laser-treated eyes, IOP was persistently elevated throughout all observation periods. PET imaging showed increased [(11)C]PK11195 binding potential in the bilateral LGN at 4 weeks after laser treatment; the increase in the ipsilateral LGN was statistically significant (P<0.05, n = 4). Immunostaining showed bilateral activations of microglia and astrocytes in LGN layers receiving input from the laser-treated eye. PBR-positive cells were observed in LGN layers receiving input from laser-treated eye at all experimental glaucoma stages including the mild glaucoma stage and their localization coincided with Iba-1 positive microglia and GFAP-positive astrocytes. These data suggest that glial activation occurs in the LGN at a mild glaucoma stage, and that the LGN degeneration could be detected by a PET imaging with [(11)C]PK11195 during the moderate experimental glaucoma stage after unilateral ocular hypertension. Therefore, activated glial markers such as PBR in the LGN may be useful in noninvasive molecular imaging for diagnosis of glaucoma.

Reversible hemianopsia caused by mechanical compression of the visual pathway by the dilated draining vein of an arteriovenous malformation--case report.

A 41-year-old woman presented with progressive hemianopsia caused by compression of the lateral geniculate body by the dilated basal vein draining a contralateral frontal arteriovenous malformation (AVM). Magnetic resonance (MR) imaging revealed left frontal AVM and right lateral geniculate body compression due to the dilated basal vein. Emergent presurgical transarterial embolization and surgical removal were performed. Left hemianopsia completely recovered 3 months after surgery and MR imaging indicated improvement of the compression of the lateral geniculate body. Direct mechanical compression of the enlarged drainage vein is one of the causes of homonymous hemianopsia. Early surgical treatment is recommended to obtain a rapid recovery.

Characterization of REM-sleep associated ponto-geniculo-occipital waves in the human pons.

STUDY OBJECTIVES: Ponto-geniculo-occipital (PGO) waves are phasic pontine, lateral geniculate, and cortical field potentials occurring during and before REM sleep that are proposed to mediate a wide variety of sleep related neural processes. We sought to identify and characterize human PGO waves. DESIGN: We recorded simultaneously from intrapontine depth electrodes and scalp electrodes in a human subject across sleep states. SETTING: Tertiary care neurological and neurosurgical referral center. PATIENTS OR PARTICIPANTS: We studied a patient involved in a study of the clinical effects of unilateral pedunculopontine nucleus (PPN) stimulation on Parkinson disease (PD). INTERVENTIONS: No interventions. MEASUREMENTS AND RESULTS: We recorded phasic potentials from the human pons occurring during and before REM sleep with a morphology, temporal distribution, and localization similar to those of PGO waves in other mammals. The source of these potentials was localized to a circumscribed region of the pontomesencephalic tegmentum. These potentials were only incompletely associated with eye movements. They were followed by characteristic cortical potentials with a latency of 20-140 msec. CONCLUSIONS: We conclude that PGO waves are a feature of human REM sleep, that they are generated or propagated in the pontomesencephalic tegmentum, that they are only partially associated with eye movements, and that they are associated with characteristic changes in cortical activity.

Remodeling of synaptic structure in sensory cortical areas in vivo.

Although plastic changes are known to occur in developing and adult cortex, it remains unclear whether these changes require remodeling of cortical circuitry whereby synapses are formed and eliminated or whether they rely on changes in the strength of existing synapses. To determine the structural stability of dendritic spines and axon terminals in vivo, we chose two approaches. First, we performed time-lapse two-photon imaging of dendritic spine motility of layer 5 pyramidal neurons in juvenile [postnatal day 28 (P28)] mice in visual, auditory, and somatosensory cortices. We found that there were differences in basal rates of dendritic spine motility of the same neuron type in different cortices, with visual cortex exhibiting the least structural dynamics. Rewiring visual input into the auditory cortex at birth, however, failed to alter dendritic spine motility, suggesting that structural plasticity rates might be intrinsic to the cortical region. Second, we investigated the persistence of both the presynaptic (axon terminals) and postsynaptic (dendritic spine) structures in young adult mice (P40-P61), using chronic in vivo two-photon imaging in different sensory areas. Both terminals and spines were relatively stable, with >80% persisting over a 3 week period in all sensory regions. Axon terminals were more stable than dendritic spines. These data suggest that changes in network function during adult learning and memory might occur through changes in the strength and efficacy of existing synapses as well as some remodeling of connectivity through the loss and gain of synapses.

Optic radiations: a microsurgical anatomical study.

OBJECT: In this study, the authors used a fiber-dissection technique to describe the optic radiation. They focused on the morphological characteristics (length and breadth) of this structure, its course, and its relationships with neighboring fasciculi and the lateral ventricle. METHODS: The authors dissected 10 previously frozen, formalin-fixed human brains with the aid of an operating microscope by following the fiber dissection technique described by Klingler in 1960. Lateral, inferior, and medial approaches were made. The optic radiation, also known as the Gratiolet radiation, extended from the lateral geniculate body to the calcarine fissure. The average distance from the tip of the anterior Meyer loop to the calcarine sulcus was 105 mm (range 95-114 mm). The breadth of the optic radiations, one on each side of the brain, averaged 17 mm at the level of the inferior horn (range 15-18 mm). This tract could be divided into three main segments: the anterior or Meyer loop, the body, and the end of the optic radiation. Adjacent anatomical structures included: laterally, the inferior longitudinal fasciculi; medially, the tapetum of the corpus callosum; and the ependyma of the inferior horn of the lateral ventricle. CONCLUSIONS: Various practical surgical approaches are discussed. The knowledge gained by studying this particular anatomy will help prevent injury to the optic radiations during neurosurgery.

Automated classification of peripheral distal by-pass geometries reconstructed from medical data.

Abnormal haemodynamic conditions are implicated in the development of anastomotic myointimal hyperplasia (MIH). However, these conditions are difficult to determine in vivo, prompting research using ex vivo idealised models. To relate the understanding gained in idealised geometries to anatomically correct conditions we have investigated a reproducible approach to classify in vivo distal graft anastomoses and their inter-patient variability. In vivo distal anastomotic geometries were acquired by magnetic resonance (MR) angiography from 13 patients who had undergone infrageniculate autologous venous by-pass surgery. On average, the images were acquired 2 weeks post-operatively. Five patients also underwent repeat examinations 2 to 7 weeks later. For each geometry, the surface of the arterial lumen is represented by the zero level set of an implicit function constructed from radial basis functions that minimise curvature. The three-dimensional binary image created from the interpolated surface is processed using a skeletonisation algorithm to obtain the centreline of each branch in the geometry. This allows for the measurement of the branching angles between straight line approximations of the centrelines of each vessel, averaging them over a characteristic length of each anastomosis. The main finding in the application of the proposed classification methodology to this set of patients is that the spectrum of anastomoses can be reduced to a small subset of cases characterised by two angles: the angle between the graft and the plane of the host artery and the angle between the graft and the proximal branch of the artery.

Inhibition of hibernation by exercise is not affected by intergeniculate leaflets lesion in hamsters.

The circadian clock of mammals, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, has been demonstrated to integrate day length change from long (LP) to short photoperiod (SP). This photoperiodic change induces in Syrian hamsters a testicular regression through melatonin action, a phenomenon that is inhibited when hamsters have free access to a wheel. The intergeniculate leaflets (IGL), which modulate the integration of photoperiod by the SCN, are a key structure in the circadian system, conveying nonphotic information such as those induced by novelty-induced wheel running activity. We tested in hamsters transferred from LP to a cold SP the effects of wheel running activity on a photoperiod-dependent behavior, hibernation. Lesions of the IGL were done to test the role of this structure in the inhibition induced by exercise of photoperiod integration by the clock. We show that wheel running activity actually inhibits hibernation not only in sham-operated animals, but also in hamsters with a bilateral IGL lesion (IGLX). In contrast, IGL-X hamsters without a wheel integrate slower to the SP but hibernate earlier compared with sham-operated animals. Moreover, some hibernation characteristics are affected by IGL lesion. Throughout the experiment at 7 degrees C, IGL-X hamsters were in hypothermia during 18% of the experiment vs. 32% for sham-operated hamsters. Taken together, these data show that the IGL play a modulatory role in the integration of photoperiodic cues and modulate hibernation, but they are not implicated in the inhibition of hibernation induced by wheel running activity.

Behavioral responses to light in mice with dorsal lateral geniculate lesions.

Light has rapid direct effects on behavior and physiology that may be distinguished from its indirect effects that occur via synchronization of the biological clock. In nocturnal animals, light at night acutely suppresses the wheel running activity usually observed at that time of day. This is known as masking because light masks the overt expression of the circadian activity rhythm. In the present study, we compared the effects of light on wheel running in mice with bilateral electrolytic lesions of the dorsal lateral geniculate nucleus (DLG) to those in sham-operated animals. DLG-lesioned animals exhibited greater suppression of wheel running in response to bright light than did the controls, but failed to exhibit the increased activity in response to dim light observed in intact animals. These findings support the view that masking effects of light on behavior comprise two opposing processes, one that increases activity and is mediated by the classical visual system, and another that suppresses activity and is mediated by a non image-forming irradiance detection system.

Intergeniculate leaflets lesion delays but does not prevent the integration of photoperiodic change by the suprachiasmatic nuclei.

The duration of the photosensitive phase of the suprachiasmatic nuclei (SCN), as revealed by light-induced Fos protein expression, depends on the photoperiod and is tied to the length of the night. We show here in Syrian hamsters that after a transfer from long to short photoperiod, lengthening of the photosensitive phase of the SCN is significantly delayed but not abolished when the intergeniculate leaflets (IGL) are lesioned. Thus IGL modulate the integration by the SCN of a photoperiodic change.

Long-term changes in middle latency response and evidence of retrograde degeneration in the medial geniculate body after auditory cortical ablation in cats.

Short- and long-term changes in the middle latency response (MLR) after bilateral ablation of the auditory cortices were studied in awake cats. The amplitude of the negative peak with a latency of about 15 ms (NA) decreased to 60% of the original value 1 week after ablation (short-term change). In the long term, i.e. 11-30 months, NA either decreased further (decreased group) or remained unchanged (non-decreased group). A histological study with light microscopy revealed degeneration of neurons in the ventral nucleus of the medial geniculate body (MGv) in the decreased group, whereas the neurons in this region were preserved in the non-decreased group. This study suggests that long-term changes in NA reflect retrograde degeneration in the MGv after auditory cortical ablation.

Does the intergeniculate leaflet play a role in the integration of the photoperiod by the suprachiasmatic nucleus?

The circadian clock located in the suprachiasmatic nuclei (SCN) is influenced by the photoperiod. After the transfer from a long (LP 14:10) to a short photoperiod (SP 10:14), the adjustment of the light sensitivity of the SCN, in terms of Fos expression, takes 25 nights. To examine the contribution of the thalamic intergeniculate leaflet (IGL) and its NPY-immunoreactive projection in the extension of the duration of the photosensitive phase of the SCN, male Syrian hamsters received electrolytic lesions of the IGL. We showed a lower number of Fos-ir cells in the SCN of IGLx hamsters following a light pulse applied 13 h after dark onset, 25 nights after the transfer from LP to SP compared to sham operated hamsters. The present study shows that the integrity of the IGL is necessary to have a complete integration of photoperiodic changes by the SCN. This demonstrates the involvement of the IGL in the integration of photoperiodic information by the SCN.

An integrated multipurpose lesion-making electrode.

PURPOSE: Although excellent results are reported from centers using microelectrode mapping during stereotactic pallidotomy, the recording methods used are time-consuming and technically cumbersome. We sought to develop a new electrode concept that may, when eventually applied in clinical practice, improve the efficiency and safety of microelectrode-guided functional neurosurgical procedures. CONCEPT: The scout electrode uses a recently developed research technique for simultaneously obtaining multiple microelectrode recordings along the shaft of a macroelectrode. RATIONALE: By positioning recording sites on either side of a lesion-making contact, it is possible to functionally "scout" the brain tissue surrounding the proposed lesion site, thus eliminating the need for serial movements and electrode interchanges. DISCUSSION: The feasibility of the scout electrode concept was tested using prototypes placed into cat medial geniculate nucleus. High-quality unit recordings were simultaneously obtained from different regions within the medial geniculate nucleus. This ability to physiologically map sites above and below the lesion-making contact facilitated precise placement of radiofrequency lesions in the center of the medial geniculate nucleus. These results suggest that it may be possible to develop clinically useful devices based on this novel concept.

Surgical management of geniculate neuralgia.

BACKGROUND: Geniculate ganglion or nervus intermedius neuraigia is an unusual condition resulting in deep ear pain with or without signs of atypical trigeminal neuralgia, deep face, or throat pain. This article describes an experience with 14 patients who came to the neurosurgical service at the University of Pittsburgh Medical Center with a diagnosis of geniculate neuralgia. METHODS: After failing conservative treatment and after undergoing neurologic, otologic, and dental evaluations, these 14 patients underwent 20 intracranial procedures consisting of retromastoid craniectomies with microvascular decompression of cranial nerves V, IX, and X with section of the nervus intermedius in most cases. RESULTS: At operation, vascular compression of the nerves and nervus intermedius was found, which implicated vascular compression as an etiology of this disorder. Initially, 10 of 14 patients had an excellent outcome (71.5%), 3 experienced partial relief (21.5%), and there was 1 failure (7%). Ten patients were available for long-term (> 12 months) follow-up. Of these 10, 3 retained the excellent result (30%), 6 experienced partial relief (60%), and there was 1 failure (10%). Complications included one transient facial paresis, one facial numbness, one paresis of cranial nerves IX and X, one chemical meningitis, two cerebrospinal fluid leaks, and one superficial wound infection. Of those that fell from the excellent to partial category, this usually involved a return of atypical facial pain, but otalgia remained resolved. CONCLUSIONS: Overall, good results (with excellent or partial relief) were found long term for 90% of patients in this series. The authors recommend microvascular decompression of cranial nerves V, IX, and X with nervus intermedius section for the treatment of geniculate neuralgia.

Growth of optic tract axons in nerve grafts in hamsters.

Segments of peripheral nerve, transplanted to the brain or spinal cord, recently have been shown to support regeneration of axons from a variety of central neurons. However, long-tract axons, injured at considerable distances from their cell bodies, have proven refractory to such regenerative support. This report presents evidence for successful, although similarly limited, growth of retinal ganglion cell axons into peripheral nerve grafts placed in the optic tract of adult hamsters. The demonstration of such growth allows the possibility that the primary visual pathways may serve as an advantageous model system in which to study the mechanism of graft-effected regeneration of long-tract axons in the adult mammalian central nervous system.