Neonatal Rats Exhibit a Predominantly Anti-Inflammatory Response following Spinal Cord Injury

It has been reported that children may respond better than adults to a spinal cord injury (SCI) of similar severity. There are known biomechanical differences in the developing spinal cord that may contribute to this “infant lesion effect,” but the underlying mechanisms are unknown. Using immunohistochemistry, we have previously demonstrated a different injury progression and immune cell response after a mild thoracic contusion SCI in infant rats, as compared to adult rats. Here, we investigated the acute inflammatory responses using flow cytometry and ELISA at 1 h, 24 h, and 1 week after SCI in neonatal (P7) and adult (9 weeks) rats, and locomotor recovery was examined for 6 weeks after injury. Adult rats exhibited a pronounced pro-inflammatory response characterized by neutrophils and M1-like macrophage infiltration and Th1 cytokine secretion. Neonatal rats exhibited a decreased pro-inflammatory response characterized by a higher proportion of M2-like macrophages and reduced Th1 cytokine responses, as compared to adults. These results suggest that the initial inflammatory response to SCI is predominantly anti-inflammatory in very young animals.

Corneal endothelial cell loss after trabeculectomy and phacoemulsification in one or two steps: a prospective study

Objective The objective of this study was to analyse the results of the surgical treatment of coexisting cataract and glaucoma and its effects on corneal endothelial cell density (CECD). Methods We include two longitudinal prospective studies: one randomised that included 40 eyes with open angle glaucoma that received one- (n = 20) or two-step (n = 20) phacotrabeculectomy and another that included 20 eyes that received phacoemulsification. We assess the impact of surgery on different clinical variables and in particular in CECD using Confoscan 4™ confocal microscopy and semiautomatic counting methods. Results Phacoemulsification and phacotrabeculectomy, but not trabeculectomy, increase significantly best-corrected visual acuity and anterior chamber depth and trabeculectomy and one- or two-step phacotrabeculectomy decreased similarly the intraocular pressure. We document percentages of endothelial cell loss of 3.1%, 17.9%, 31.6% and 42.6% after trabeculectomy, phacoemulsification and one- or two-step phacotrabeculectomy, respectively. The coefficient of variation did not increase significantly after surgery but the percentage of hexagonality decreased significantly after phacoemulsification and after two-step phacotrabeculectomy. Conclusions Trabeculectomy, phacoemulsification and phacotrabeculectomy are surgical techniques that cause morphological changes and decrease the densities of the corneal endothelial cells. Trabeculectomy produces lesser endothelial cell loss than phacoemulsification, and phacoemulsification lesser cell loss than phacotrabeculectomy. Two-step phacotrabeculectomy (trabeculectomy followed 3 months later by phacoemulsification) causes more cell loss than one-step phacotrabeculectomy, and this could be due to the cumulative effects of two separate surgical traumas or to a negative conditioning lesion effect of the first surgery. For the treatment of coexisting glaucoma and cataract, one-step phacotrabeculectomy is the treatment of choice.

Paradoxical lesions, plasticity and active inference

Paradoxical lesions are secondary brain lesions that ameliorate functional deficits caused by the initial insult. This effect has been explained in several ways; particularly by the reduction of functional inhibition, or by increases in the excitatory-to-inhibitory synaptic balance within perilesional tissue. In this article, we simulate how and when a modification of the excitatory–inhibitory balance triggers the reversal of a functional deficit caused by a primary lesion. For this, we introduce in-silico lesions to an active inference model of auditory word repetition. The first in-silico lesion simulated damage to the extrinsic (between regions) connectivity causing a functional deficit that did not fully resolve over 100 trials of a word repetition task. The second lesion was implemented in the intrinsic (within region) connectivity, compromising the model’s ability to rebalance excitatory–inhibitory connections during learning. We found that when the second lesion was mild, there was an increase in experience-dependent plasticity that enhanced performance relative to a single lesion. This paradoxical lesion effect disappeared when the second lesion was more severe because plasticity-related changes were disproportionately amplified in the intrinsic connectivity, relative to lesioned extrinsic connections. Finally, this framework was used to predict the physiological correlates of paradoxical lesions. This formal approach provides new insights into the computational and neurophysiological mechanisms that allow some patients to recover after large or multiple lesions.

Botulinum Toxin Conditioning Enhances Motor Axon Regeneration in Mouse and Human Preclinical Models

Background. Peripheral axon regeneration is improved when the nerve lesion under consideration has recently been preceded by another nerve injury. This is known as the conditioning lesion effect (CLE). While the CLE is one of the most robust and well characterized means to enhance motor axon regeneration in experimental models, it is not considered a clinically feasible strategy. A pharmacological means to re-produce the CLE is highly desirable. Objective. To test whether chemodenervation with a clinical grade formulation of botulinum toxin A (BoTX) would be sufficient to reproduce the CLE. Methods. We examined the effects of a 1-week preconditioning administration of BoTX on motor axon regrowth in both a mouse tibial nerve injury and human embryonic stem cell (hESC)–based model. We assessed neuronal reinnervation in vivo (mice) with retrograde tracers and histological analysis of peripheral nerve tissue after injections into the triceps surae muscle group. We assessed motor neuron neurite outgrowth in vitro (hESC) after incubation in BoTX by immunohistochemistry and morphometric analysis. Results. We found that BoTX conditioning treatment significantly enhanced outgrowth of both murine motor axons in vivo and human MN neurites in vitro. Conclusions. BoTX preconditioning represents a pharmacological candidate approach to enhance motor axon regeneration in specific clinical scenarios such as nerve transfer surgery. Further studies are needed to elucidate the molecular mechanism.

Frequent vomiting attacks in a patient with Lhermitte-Duclos disease: a rare pathophysiology of cerebellar lesions?

Lhermitte-Duclos disease (LDD) is a neurological disease caused by a hamartomatous lesion in the cerebellum. Clinically, LDD is commonly associated with progressive space-occupying lesion effects in the posterior fossa, increasing intracranial pressure, occlusive hydrocephalus, and focal neurological deficits of adjacent structures. The authors report the case of a 10-year-old boy with LDD who had been suffering from vomiting attacks (VAs). These VAs had been brief in duration but extremely frequent, and they had been resistant to antiemetic drugs since the early postnatal period. Magnetic resonance imaging at 8 months of age revealed a right cerebellar lesion with very little space-occupying lesion effect, but the causal relationship with VAs was not evident at that point, because no clinical symptoms or signs other than vomiting were suggestive of increased intracranial pressure. The VAs were initially diagnosed as autonomic ataxia and had been treated with antiemetic drugs for approximately 10 years, but the patient’s symptoms were not improved at all in frequency or duration. He developed convulsive seizures at 9 years of age and was referred to the authors’ epilepsy center. The VAs were initially speculated to represent an aspect of seizures, but antiepileptic agents proved ineffective against this symptom despite remission of convulsive seizures. Video-electroencephalography monitoring did not show any evolving ictal patterns associated with the vomiting. Careful reevaluation of MRI studies revealed that the cerebellar lesion was fused with the cerebellum, middle and inferior cerebellar peduncles, and dorsolateral medulla oblongata with some distortion. FDG-PET identified hypermetabolism in the cerebellar lesion. After establishing the diagnosis of LDD, the authors performed subtotal resection of the lesion based on the likelihood of a causal relationship between the cerebellar lesion and the vomiting center of the medulla oblongata. Postoperatively and for 2 years, VAs have remained completely suppressed. The authors hypothesize that the pathophysiology of VAs in LDD includes a tumor-like space-occupying effect on the vomiting center of the medulla oblongata, and even partial resection of the lesion may prove effective.

Deep brain stimulation of the ventralis intermedius nucleus for the treatment of essential tremor

A 59-year-old woman with a 30-year history of essential tremor refractory to medical therapy underwent staged deep brain stimulation of the ventralis intermedius nucleus of the thalamus (VIM). Left-sided lead placement was performed first. Once in the operating room, microelectrode recording (MER) was performed to confirm the appropriate trajectory and identify the VIM border with the ventralis caudalis nucleus. MER was repeated after repositioning 2 mm anteriorly to reduce the likelihood of stimulation-induced paresthesias. Physical examination prior to permanent lead placement demonstrated micro-lesion effect, suggesting optimal trajectory. After implantation of the permanent lead, physical examination showed excellent results.The video can be found here: https://youtu.be/nn3KRdmRCZ4.