Lithium treatment reverses irradiation-induced changes in rodent neural progenitors and rescues cognition.

Cranial radiotherapy in children has detrimental effects on cognition, mood, and social competence in young cancer survivors. Treatments harnessing hippocampal neurogenesis are currently of great relevance in this context. Lithium, a well-known mood stabilizer, has both neuroprotective, pro-neurogenic as well as antitumor effects, and in the current study we introduced lithium treatment 4 weeks after irradiation.

The Secretome of Microglia Regulate Neural Stem Cell Function.

Brain injury is associated with neuroinflammation, and microglia are key players in this process. Microglia can acquire pro-inflammatory or anti-inflammatory properties, but how this affects neural stem cells (NSCs) remains controversial. Here, NSCs were grown in conditioned media collected from either non-stimulated microglia, or microglia stimulated with pro- or anti-inflammatory agents.

Cranial irradiation induces transient microglia accumulation, followed by long-lasting inflammation and loss of microglia.

The relative contribution of resident microglia and peripheral monocyte-derived macrophages in neuroinflammation after cranial irradiation is not known. A single dose of 8 Gy was administered to postnatal day 10 (juvenile) or 90 (adult) CX3CR1GFP/+ CCR2RFP/+ mouse brains. Microglia accumulated in the subgranular zone of the hippocampal granule cell layer, where progenitor cell death was prominent.

Complement receptor 2 is up regulated in the spinal cord following nerve root injury and modulates the spinal cord response.

Background: Activation of the complement system has been implicated in both acute and chronic states of neurodegeneration. However, a detailed understanding of this complex network of interacting components is still lacking.

Methods: Large-scale global expression profiling in a rat F2(DAxPVG) intercross identified a strong cis-regulatory influence on the local expression of complement receptor 2 (Cr2) in the spinal cord after ventral root avulsion (VRA).

Variability in C-type lectin receptors regulates neuropathic pain-like behavior after peripheral nerve injury.

Introduction: Neuropathic pain is believed to be influenced in part by inflammatory processes. In this study we examined the effect of variability in the C-type lectin gene cluster (Aplec) on the development of neuropathic pain-like behavior after ligation of the L5 spinal nerve in the inbred DA and the congenic Aplec strains, which carries seven C-type lectin genes originating from the PVG strain.

Results: While both strains displayed neuropathic pain behavior early after injury, the Aplec strain remained sensitive throughout the whole study period.

Unbiased expression mapping identifies a link between the complement and cholinergic systems in the rat central nervous system.

The complement system is activated in a wide spectrum of CNS diseases and is suggested to play a role in degenerative phenomena such as elimination of synaptic terminals. Still, little is known of mechanisms regulating complement activation in the CNS. Loss of synaptic terminals in the spinal cord after an experimental nerve injury is increased in the inbred DA strain compared with the PVG strain and is associated with expression of the upstream complement components C1q and C3, in the absence of membrane attack complex activation and neutrophil infiltration.

Genetic variability in the rat Aplec C-type lectin gene cluster regulates lymphocyte trafficking and motor neuron survival after traumatic nerve root injury.

Background: C-type lectin (CLEC) receptors are important for initiating and shaping immune responses; however, their role in inflammatory reactions in the central nervous system after traumatic injuries is not known. The antigen-presenting lectin-like receptor gene complex (Aplec) contains a few CLEC genes, which differ genetically among inbred rat strains. It was originally thought to be a region that regulates susceptibility to autoimmune arthritis, autoimmune neuroinflammation and infection.

The DQB1 *03:02 HLA haplotype is associated with increased risk of chronic pain after inguinal hernia surgery and lumbar disc herniation.

Neuropathic pain conditions are common after nerve injuries and are suggested to be regulated in part by genetic factors. We have previously demonstrated a strong genetic influence of the rat major histocompatibility complex on development of neuropathic pain behavior after peripheral nerve injury. In order to study if the corresponding human leukocyte antigen complex (HLA) also influences susceptibility to pain, we performed an association study in patients that had undergone surgery for inguinal hernia (n=189).

Sex differences in the development of localized and spread mechanical hypersensitivity in rats after injury to the infraorbital or sciatic nerves to create a model for neuropathic pain.

Background: Neuropathic pain after injury to the nervous system is a difficult clinical problem. Sex differences in the development of neuropathic pain have not been well established experimentally or clinically.

Objective: Rats were used to examine sex differences in localized and spread mechanical hypersensitivity after partial injury to their infraorbital or sciatic nerves in a model of neuropathic pain.

Contrasting genetic effects of major histocompatibility complex on ischemic peripheral nerve and spinal cord injury in female rats.

We have recently shown that the major histocompatibility complex (MHC) exerts a regulatory influence on the development of neuropathic pain-like behaviors after partial sciatic nerve injury in male rats. In the present study, we assessed the role of the MHC in peripheral nerve injury-induced pain as well as central pain following spinal cord injury in female rats using the following inbred strains: Dark Agouti (DA; RT1(av1)), Piebald Virol Glaxo (PVG; RT1(c)) and in the MHC-congenic strain PVG-RT1(av1). In line with our previous observation in male rats, PVG-RT1(c) displayed more severe allodynia compared to the strains carrying the RT1(av1) haplotype (PVG-RT1(av1) and DA-RT1(av1)) following sciatic nerve injury in female rats.

Both MHC and non-MHC genes regulate development of experimental neuropathic pain in rats.

We have previously demonstrated that differences in neuropathic pain-like behaviors after sciatic nerve injury genetically maps to the major histocompatibility complex (MHC) in rats carrying RT1(c) or RT1(av1) haplotypes on the Piebald Virol Glaxo (PVG) background. In order to further explore the genetic contribution to neuropathic pain, we have here examined the MHC-congenic rat strains PVG-RT1(n) and PVG-RT1(av1) and the inbred strains PVG (RT1(c)) and Brown-Norway (BN; RT1(n)). All studied strains developed mechanical hypersensitivity (allodynia-like behavior) of the hind paw after photochemically induced sciatic nerve injury.

Genetic analysis of neuropathic pain-like behavior following peripheral nerve injury suggests a role of the major histocompatibility complex in development of allodynia.

Neuropathic pain is a common consequence of damage to the nervous system. We here report a genetic analysis of development of neuropathic pain-like behaviors after unilateral photochemically-induced ischemic sciatic nerve injury in a panel of inbred rat strains known to display different susceptibility to autoimmune neuroinflammation. Pain behavior was initially characterized in Dark-Agouti (DA; RT1(av1)), Piebald Virol Glaxo (PVG; RT1(c)), and in the major histocompatibility complex (MHC)-congenic strain PVG-RT1(av1).