Maternal Minocycline as Fetal Therapy in a Rat Model of Myelomeningocele.

INTRODUCTION: This study aimed to investigate whether the maternal administration of minocycline, a tetracycline antibiotic known to have anti-inflammatory and neuroprotective properties in models of neural injury, reduces inflammation and neural cell death in a fetal rat model of myelomeningocele (MMC). METHODS: E10 pregnant rats were gavaged with olive oil or olive oil + retinoic acid to induce fetal MMC. At E12, the dams were exposed to regular drinking water or water containing minocycline (range, 40-140 mg/kg/day). At E21, fetal lumbosacral spinal cords were isolated for immunohistochemistry and quantitative gene expression studies focused on microglia activity, inflammation, and apoptosis (P < 0.05). RESULTS: There was a trend toward decreased activated Iba1+ microglial cells within the dorsal spinal cord of MMC pups following minocycline exposure when compared to water (H2O) alone (P = 0.052). Prenatal minocycline exposure was correlated with significantly reduced expression of the proinflammatory cytokine, IL-6 (minocycline: 1.75 versus H2O: 3.52, P = 0.04) and apoptosis gene, Bax (minocycline: 0.71 versus H2O: 1.04, P < 0.001) among MMC pups. CONCLUSIONS: This study found evidence that the maternal administration of minocycline reduces selected markers of inflammation and apoptosis within the exposed dorsal spinal cords of fetal MMC rats. Further study of minocycline as a novel prenatal treatment strategy to mitigate spinal cord damage in MMC is warranted.

[Spondylodiscitis and epidural abscesses]. / Spondylodiszitis und epiduraler Abszess.

CLINICAL/METHODOLOGICAL PROBLEM: Spondylodiscitis is an inflammation of the intervertebral disc, which in adults is generally associated with spondylitis of the adjacent vertebrae. It often presents clinically with nonspecific symptoms such as back or neck pain. It may be caused by various pathogens, especially bacteria. One or more vertebral segments can be affected. The infection can spread to surrounding compartments and can lead to epidural abscesses. Radiology, in particular magnetic resonance imaging (MRI), plays an important role in the diagnostic work-up and in the follow-up to monitor response to therapy. Treatment consists of conservative (antibiotics) and invasive approaches, including surgery. Interventional puncture and drainage is a promising alternative to surgery, especially in early stages of abscess formation. STANDARD RADIOLOGICAL METHODS: Magnetic resonance imaging (MRI), computed tomography (CT), nuclear medical procedures, conventional x­ray. PERFORMANCE: MRI has the highest value. CT and nuclear medical procedures can be used as a supplement to MRI and in patients with contraindications for MRI. PRACTICAL RECOMMENDATIONS: With adequate diagnosis and therapy, spondylodiscitis has a good prognosis. In addition to targeted or calculated drug therapy, invasive treatment is the main focus, especially for epidural abscesses. Interventional radiological drainage can represent a less invasive alternative to surgical treatment.

Systemic Lipopolysaccharide-Induced Pain Sensitivity and Spinal Inflammation Were Reduced by Minocycline in Neonatal Rats.

In this study, we investigated the effects of minocycline, a putative suppressor of microglial activation, on systemic lipopolysaccharide (LPS)-induced spinal cord inflammation, allodynia, and hyperalgesia in neonatal rats. Intraperitoneal (i.p.) injection of LPS (2 mg/kg) or sterile saline was performed in postnatal day 5 (P5) rat pups and minocycline (45 mg/kg) or vehicle (phosphate buffer saline; PBS) was administered (i.p.) 5 min after LPS injection. The von Frey filament and tail-flick tests were performed to determine mechanical allodynia (a painful sensation caused by innocuous stimuli, e.g., light touch) and thermal hyperalgesia (a condition of altered perception of temperature), respectively, and spinal cord inflammation was examined 24 h after the administration of drugs. Systemic LPS administration resulted in a reduction of tactile threshold in the von Frey filament tests and pain response latency in the tail-flick test of neonatal rats. The levels of microglia and astrocyte activation, pro-inflammatory cytokine interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) in the spinal cord of neonatal rats were increased 24 h after the administration of LPS. Treatment with minocycline significantly attenuated LPS-induced allodynia, hyperalgesia, the increase in spinal cord microglia, and astrocyte activation, and elevated levels of IL-1ß, COX-2, and PGE2 in neonatal rats. These results suggest that minocycline provides protection against neonatal systemic LPS exposure-induced enhanced pain sensitivity (allodynia and hyperalgesia), and that the protective effects may be associated with its ability to attenuate LPS-induced microglia activation, and the levels of IL-1ß, COX-2, and PGE2 in the spinal cord of neonatal rats.

Severe Spinal Cord Inflammation in a Young Woman Diagnosed With Systemic Lupus Erythematosus: A Case Study.

We describe a case of longitudinally extensive transverse myelitis (LETM), an uncommon and dangerous complication of systemic lupus erythematosus (SLE) that struck a 22-year-old woman with SLE. Chronic autoimmune illness (e.g., SLE) affects the skin, kidneys, joints, blood, and neurological system, among other organs. LETM is a condition where the spinal cord becomes inflamed and damaged, causing neurological problems, such as weakness, sensory loss, and bladder dysfunction. The patient presented with abdominal pain, vomiting, body aches, and fatigue, followed by shock, hypoxia, urinary retention, and constipation. Moreover, she had severe and asymmetric weakness, sensory loss, and areflexia in her limbs. She was diagnosed with LETM based on a nerve conduction study and MRI of the spine, which showed a motor neuron disease pattern and T2 hyperintense signals throughout the spinal cord gray and white matter. She responded well to immunoglobulins, plasma exchange, and high-dose steroids as treatment. Although her prognosis is favorable, there might be some lingering neurological issues or limitations. This instance highlights the significance of treating individuals with SLE as soon as possible after developing LETM.

An Aberrant Case of Neuromyelitis Optica Spectrum Disorder With a Review of Literature.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, acquired demyelinating condition predominantly affecting middle-aged women and is characterized by spinal cord inflammation and optic neuritis. Anti-aquaporin 4 (AQP4) antibodies are typically seen in NMOSD. However, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) shares clinical and imaging similarities. In NMOSD, longitudinally extensive spinal cord lesions (LESCLs), optic neuritis predominantly affecting the posterior aspect of optic nerves, and optic radiations are seen on magnetic resonance imaging (MRI). The brain parenchymal lesions particularly involve the dorsal medulla (area postrema). The report presents a case of a 26-year-old female with recurrent episodes of weakness, pain, and sensory symptoms in both upper and lower limbs who was initially treated for multiple sclerosis. Upon experiencing new symptoms of blurred vision and ataxia, an MRI of the spine and brain was performed, which showed short-segment cervical cord involvement and a lesion in the conus medullaris, raising the suspicion of NMOSD. Subsequent antibody testing confirmed the presence of anti-AQP4 antibodies. While the involvement of the conus medullaris is classically associated with MOGAD, unusual findings in the present case highlight the importance of comprehensive imaging evaluation and raising awareness among clinicians and radiologists regarding the imaging spectrum of NMOSD, thus facilitating timely diagnosis and tailored treatment strategies.

Delayed onset of inherited ALS by deletion of the BDNF receptor TrkB.T1 is non-cell autonomous.

The pathophysiology of Amyotrophic Lateral Sclerosis (ALS), a disease caused by the gradual degeneration of motoneurons, is still largely unknown. Insufficient neurotrophic support has been cited as one of the causes of motoneuron cell death. Neurotrophic factors such as BDNF have been evaluated in ALS human clinical trials, but yielded disappointing results attributed to the poor pharmacokinetics and pharmacodynamics of BDNF. In the inherited ALS G93A SOD1 animal model, deletion of the BDNF receptor TrkB.T1 delays spinal cord motoneuron cell death and muscle weakness through an unknown cellular mechanism. Here we show that TrkB.T1 is expressed ubiquitously in the spinal cord and its deletion does not change the SOD1 mutant spinal cord inflammatory state suggesting that TrkB.T1 does not influence microglia or astrocyte activation. Although TrkB.T1 knockout in astrocytes preserves muscle strength and co-ordination at early stages of disease, its specific conditional deletion in motoneurons or astrocytes does not delay motoneuron cell death during the early stage of the disease. These data suggest that TrkB.T1 may limit the neuroprotective BDNF signaling to motoneurons via a non-cell autonomous mechanism providing new understanding into the reasons for past clinical failures and insights into the design of future clinical trials employing TrkB agonists in ALS.

Prognostic Parameters of Acute Transverse Myelitis in Children.

Acute transverse myelitis is a rare and disabling disorder. Data on the imaging features in children are sparse. The aim of this study was to describe the clinical and magnetic resonance imaging findings characteristic of pediatric idiopathic acute transverse myelitis and to identify those with prognostic value. The database of a tertiary pediatric medical center was retrospectively reviewed for patients aged less than 18 years who were diagnosed in 2002-2017 with acute transverse myelitis that was not associated with recurrence of a demyelinating autoimmune event. Data were collected on clinical, laboratory, and imaging findings and outcome. A total of 23 children (11 male, 12 female) met the study criteria. Mean age at disease onset was 10 years, and mean duration of follow-up was 6 years 10 months. Spinal cord and brain magnetic resonance imaging scans were performed on admission or shortly thereafter. The most common finding was cross-sectional involvement, in 16 patients (70%). The mean number of involved spinal segments was 8. The most frequently involved region was the thoracic spine, in 17 patients (74%). Clinical factors predicting good prognosis were cerebrospinal fluid pleocytosis, absence of tetraparesis, and prolonged time to nadir. In conclusion, most children with acute transverse myelitis appear to have a good outcome. Prompt diagnosis and treatment are important. Further research is needed in a larger sample to evaluate the predictive value of imaging features.

Interleukin-1 receptor antagonist ameliorates the pain hypersensitivity, spinal inflammation and oxidative stress induced by systemic lipopolysaccharide in neonatal rats.

Perinatal inflammation-induced reduction in pain threshold may alter pain sensitivity to hyperalgesia or allodynia which may persist into adulthood. In this study, we investigated the anti-inflammatory protective effect of interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory cytokine, on systemic lipopolysaccharide (LPS)-induced spinal cord inflammation and oxidative stress, thermal hyperalgesia, and mechanical allodynia in neonatal rats. Intraperitoneal (i.p.) injection of LPS (2 mg/kg) or sterile saline was performed in postnatal day 5 (P5) rat pups, and IL-1ra (100 mg/kg) or saline was administered (i.p.) 5 min after LPS injection. Pain reflex behavior, spinal cord inflammation and oxidative stress were examined 24 h after LPS administration. Systemic LPS exposure led to a reduction of tactile threshold in the von Frey filament tests (mechanical allodynia) and pain response latency in the tail-flick test (thermal hyperalgesia) of P6 neonatal rats. Spinal cord inflammation was indicated by the increased numbers of activated glial cells including microglia (Iba1+) and astrocytes (GFAP+), and elevated levels of pro-inflammatory cytokine interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) 24 h after LPS treatment. LPS treatment induced spinal oxidative stress as evidenced by the increase in thiobarbituric acid reactive substances (TBARS) content in the spinal cord. LPS exposure also led to a significant increase in oligodendrocyte lineage population (Olig2+) and mature oligodendrocyte cells (APC+) in the neonatal rat spinal cord. IL-1ra treatment significantly reduced LPS-induced effects including hyperalgesia, allodynia, the increased number of activated microglia, astrocytes and oligodendrocytes, and elevated levels of IL-1ß, COX-2, PGE2, and lipid peroxidation (TBARS) in the neonatal rat spinal cord. These data suggest that IL-1ra provides a protective effect against the development of pain hypersensitivity, spinal cord inflammation and oxidative stress in the neonatal rats following LPS exposure, which may be associated with the blockade of LPS-induced pro-inflammatory cytokine IL-1ß.

Spinal cord injury: From inflammation to glial scar.

BACKGROUND: Glial scar (GS) is the most important inhibitor factor to neuroregeneration after spinal cord injury (SCI) and behaves as a tertiary lesion. The present review of the literature searched for representative studies concerning GS and therapeutic strategies to neuroregeneration. METHODS: The author used the PubMed database and Google scholar to search articles published in the last 20 years. Key words used were SCI, spinal cord (SC) inflammation, GS, and SCI treatment. RESULTS: Both inflammation and GS are considered important events after SCI. Despite the fact that firstly they seem to cause benefit, in the end they cause more harm than good to neuroregeneration. Each stage has its own aspects under the influence of the immune system causing inflammation, from the primary to secondary lesion and from those to GS (tertiary lesion). CONCLUSION: Future studies should stress the key points where and when GS presents itself as an inhibitory factor to neuroregeneration. Considering GS as an important event after SCI, the author defends GS as being a tertiary lesion. Current strategies are presented with emphasis on stem cells and drug therapy. A better understanding will permit the development of a therapeutic basis in the treatment of the SCI patients considering each stage of the lesion, with emphasis on GS and neuroregeneration.