Ventral Intrameningeal Cyst Treatment and Management: Technical Note.

BACKGROUND: Intrameningeal cysts are rare lesions without definitive etiologies that can involve the dura or arachnoid mater. Spinal arachnoid cysts have been described, and several different etiologies have been hypothesized. This includes one-way valve mechanisms, traumatic herniation of arachnoid through the dura, and abnormal arachnoid membrane proliferation. To the authors' knowledge, no such descriptions exist regarding purely dural-based cystic lesions; however, the authors hypothesize similar mechanisms may be involved. Most notably, a traumatic injury to the dura leading to a one-way valve mechanism may allow for egress of cerebrospinal fluid between the dural layers, splitting them open. This progressive enlargement can lead to displacement of neural elements and subsequent neurological compromise. METHODS: We describe a 17-year-old girl who presented with progressive neck and back pain, left upper-extremity numbness, bilateral lower-extremity weakness, paresthesias, and numbness without obvious etiology despite an extensive neurologic investigation. She had undergone conservative management options including multiple medications, physical and chiropractic therapy, and epidural steroid injections. Computed tomography myelography revealed a cerebrospinal fluid leak into the lumbar epidural space for which surgical exploration was performed. Despite utilizing fluoroscopy and intrathecal fluorescein, no leak source was identified. Fluid collection was found contained within the dural layers rather than the epidural space. RESULTS: An intracystic blood patch was performed with near-complete resolution of the lesion by 6-week follow-up and near-complete return of neurologic function. CONCLUSIONS: Ventral panspinal cysts are an exceedingly rare cause of radiculopathy and myelopathy that can be resolved by an intracystic blood patch.

Cefalea pospunción dural mantenida en el tiempo / Persistent posdural puncture headache

Introducción: La cefalea posterior a la punción de la duramadre es una complicación que se describió conjuntamente con la primera anestesia neuroaxial. Es un cuadro clínico complejo, que con la terapéutica adecuada mejora rápidamente, pero en ocasiones persiste a pesar de los esfuerzos realizados por el equipo médico encargado de tratarla. Objetivo: Describir la evolución clínica de un caso cefalea pospunción dural. Discusión: Se presenta un caso que después de realizarle a una anestesia subaracnoidea para una cirugía de Hallux Varus, sufre una cefalea pospunción dural que persistió por más de 18 días, a pesar de los tratamientos impuestos, tanto conservadores (terapia farmacológica, hidratación, reposo) como intervencionista (hemoparche peridural y colchón hídrico, con dextran 40), el cuadro desapareció por si solo pasado el tiempo expuesto anteriormente. Conclusiones: Se concluye que este cuadro clínico ocasionado por la punción de la duramadre es de resolución rápida con el tratamiento adecuado, pero existen casos en los que a pesar de la terapéutica indicada puede persistir por más tiempo(AU)

Introduction: Headache after dura mater puncture is a complication described together with the first neuraxial anesthesia. A complex clinical picture improves rapidly with adequate therapy, but sometimes persists despite the efforts made by the medical team in charge of treating it. Objective: To describe the clinical evolution of case of postdural puncture headache. Discussion: A case is presented of a patient who, following subarachnoid anesthesia for hallux varus surgery, suffered postdural puncture headache that persisted for more than eighteen days, despite the treatments used, both conservative (pharmacological therapy, hydration, rest) and interventionist (peridural hemopatch and water mattress, with dextran 40). The clinical picture disappeared by itself after the time previously discussed. Conclusions: It is concluded that this clinical picture caused by the dura mater puncture is of rapid resolution if treated appropriately, but there are cases in which, despite the indicated therapy, it may persist for a longer time(AU)

Extreme Lateral Supracerebellar Infratentorial Approach: Surgical Anatomy and Review of the Literature.

OBJECTIVE: The extreme lateral supracerebellar infratentorial (ELSI) approach has the potential to access several distinct anatomical regions that are otherwise difficult to reach. We have illustrated the surgical anatomy through cadaveric dissections and provided an extensive review of the literature to highlight the versatility of this approach, its limits, and comparisons with alternative approaches. METHODS: The surgical anatomy of the ELSI has been described using 1 adult-injected cadaveric head. Formalized noninjected brain specimens were also dissected to describe the brain parenchymal anatomy of the region. An extensive review of the literature was performed according to each targeted anatomical region. Illustrative cases are also presented. RESULTS: The ELSI approach allows for wide exposure of the middle and posterolateral incisural spaces with direct access to centrally located intra-axial structures such as the splenium, pulvinar, brainstem, and mesial temporal lobe. In addition, for skull base extra-axial tumors such as petroclival meningiomas, the ELSI approach represents a rapid and adequate method of access without the use of extensive skull base approaches. CONCLUSIONS: The ELSI approach represents one of the most versatile approaches with respect to its ability to address several anatomical regions centered at the posterior and middle incisural spaces. For intra-axial pathologies, the approach allows for access to the central core of the brain with several advantages compared with alternate approaches that frequently involve significant brain retraction and cortical incisions. In specific cases of skull base lesions, the ELSI approach is an elegant alternative to traditionally used skull base approaches, thereby avoiding approach-related morbidity.

Soft tissue grafts for dural reconstruction after meningioma surgery.

The meninges are involved in various pathologies and are often directly or indirectly severed during surgical procedures, especially the dura mater. This can pose a real challenge for the surgeon, as a proper reconstruction of the meninges is important to prevent complications such as cerebrospinal fluid leak (CSF). A variety of techniques for dural reconstruction have been described, employing natural and artificial materials. A novel technique for dural reconstruction involves soft tissue grafts in the form of fibrous or fibromuscular flaps, which are placed on the dural defects to seal the gaps. These soft tissue grafts represent an appropriate scaffold for cell ingrowth and fibrosis, thus preventing CSF. In this pilot study, we described the application of soft tissue grafts for dural reconstruction in 10 patients who underwent convexity meningioma surgery.

Comparative effects of traditional Chinese and Western migraine medicines in an animal model of nociceptive trigeminovascular activation.

Background Migraine is a highly prevalent and disabling disorder of the brain with limited therapeutic options, particularly for preventive treatment. There is a need to identify novel targets and test their potential efficacy in relevant preclinical migraine models. Traditional Chinese medicines have been used for millennia and may offer avenues for exploration. Methods We evaluated two traditional Chinese medicines, gastrodin and ligustrazine, and compared them to two Western approaches with propranolol and levetiracetam, one effective and one ineffective, in an established in vivo rodent model of nociceptive durovascular trigeminal activation. Results Intravenous gastrodin (30 and 100 mg/kg) significantly inhibited nociceptive dural-evoked neuronal firing in the trigeminocervical complex. Ligustrazine (10 mg/kg) and propranolol (3 mg/kg) also significantly inhibited dural-evoked trigeminocervical complex responses, although the timing of responses of ligustrazine does not match its pharmacokinetic profile. Levetiracetam had no effects on trigeminovascular responses. Conclusion Our data suggest gastrodin has potential as an anti-migraine treatment, whereas ligustrazine seems less promising. Interestingly, in line with clinical trial data, propranolol was effective and levetiracetam not. Exploration of the mechanisms and modelling effects of Chinese traditional therapies offers novel route for drug discovery in migraine.

Long-lasting increase in axonal excitability after epidurally applied DC.

Effects of direct current (DC) on nerve fibers have primarily been investigated during or just after DC application. However, locally applied cathodal DC was recently demonstrated to increase the excitability of intraspinal preterminal axonal branches for >1 h. The aim of this study was therefore to investigate whether DC evokes a similarly long-lasting increase in the excitability of myelinated axons within the dorsal columns. The excitability of dorsal column fibers stimulated epidurally was monitored by recording compound action potentials in peripheral nerves in acute experiments in deeply anesthetized rats. The results show that 1) cathodal polarization (0.8-1.0 µA) results in a severalfold increase in the number of epidurally activated fibers and 2) the increase in the excitability appears within seconds, 3) lasts for >1 h, and 4) is activity independent, as it does not require fiber stimulation during the polarization. These features demonstrate an unexplored form of plasticity of myelinated fibers and indicate the conditions under which it develops. They also suggest that therapeutic effects of epidural stimulation may be significantly enhanced if it is combined with DC polarization. In particular, by using DC to increase the number of fibers activated by low-intensity epidural stimuli, the low clinical tolerance to higher stimulus intensities might be overcome. The activity independence of long-lasting DC effects would also allow the use of only brief periods of DC polarization preceding epidural stimulation to increase the effect.NEW & NOTEWORTHY The study indicates a new form of plasticity of myelinated fibers. The differences in time course of DC-evoked increases in the excitability of myelinated nerve fibers in the dorsal columns and in preterminal axonal branches suggest that distinct mechanisms are involved in them. The results show that combining epidural stimulation and transspinal DC polarization may dramatically improve their outcome and result in more effective pain control and the return of impaired motor functions.

Effects of Nigella sativa seeds and certain species of fungi extracts on number and activation of dural mast cells in rats.

In this study, we aimed to investigate the effects of Nigella sativa seeds and certain species of fungi extracts on the number and degranulation states of dural mast cells in rats. Rats were fed ad libitum with normal tap water or tap water with extract of N. sativa seed, Ramaria condensata, Lactarius salmonicolor, Lactarius piperatus, and Tricholoma terreum for 3 days. Mast cells in dura mater were counted and evaluated in terms of granulation and degranulation states. Compound 48/80, a mast cell degranulating agent, and T. terreum significantly increased the percent of degranulated mast cells in dura mater, respectively (p < 0.01 and p < 0.05). Moreover, T. terreum causes a significant increase in the total number of mast cells (p < 0.05). N. sativa significantly inhibited mast cell degranulation induced by both the compound 48/80 and T. terreum (p < 0.05), and significantly decreased the mast cell numbers increased by T. terreum (p < 0.05). Our results suggested that T. terreum following ingestion can contribute to headaches like migraine via dural mast cell degranulation and N. sativa may be able to exert analgesic and anti-inflammatory effects by stabilizing dural mast cells. However, investigation is needed to determine the ingredients of N. sativa that may be responsible for these beneficial effects.

Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: attenuated by KYNA derivate (SZR72).

BACKGROUND: Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund's Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72. METHODS: Activation in the trigeminal nucleus caudalis (TNC) and the trigeminal tract (Sp5) was achieved by application of CFA onto the dural parietal surface. SZR72 was given intraperitoneally (i.p.), one dose prior CFA deposition and repeatedly daily for 7 days. Immunohistochemical studies were performed for mapping glutamate, c-fos, PACAP, substance P, IL-6, IL-1ß and TNFα in the TNC/Sp5 and other regions of the brainstem and at the C1-C2 regions of the spinal cord. RESULTS: We found that CFA increased c-fos and glutamate immunoreactivity in TNC and C1-C2 neurons. This effect was mitigated by SZR72. PACAP positive fibers were detected in the fasciculus cuneatus and gracilis. Substance P, TNFα, IL-6 and IL-1ß immunopositivity were detected in fibers of Sp5 and neither of these molecules showed any change in immunoreactivity following CFA administration. CONCLUSION: This is the first study demonstrating that dural application of CFA increases the expression of c-fos and glutamate in TNC neurons. Treatment with the KYNA analogue prevented this expression.

The Effect of Ankaferd Blood Stopper? on Epidural Fibrosis After Laminectomy in Rats: An Experimental Study.

AIM: Lumbar epidural fibrosis is increasingly recognized as a cause of persistent back pain. The aim of this study was to examine the effect Ankaferd Blood Stopper on epidural fibrosis following laminectomy in rat models. MATERIAL AND METHODS: Twenty Sprague-Dawley male rats were randomly allocated to 2 groups of 10 each. The dura mater and nerve root were exposed after L1 unilateral laminectomy. Close attention was paid not to traumatize the dura, the nerve roots, or the dissected muscles. Immediate muscle and skin closure was made in sham group. In the Ankaferd Blood Stopper group, cotton wool soaked with 1 mL Ankaferd Blood Stopper was applied to the exposure site for 5 minutes, and muscle and skin closure was then made. Histological analysis was performed at four weeks postoperatively. RESULTS: Epidural fibrosis formation evaluation and fibroblastic activity evaluation revealed that there was a significant difference between the sham and the Ankaferd Blood Stopper treated groups (p = 0.011, p = 0.009). Severe epidural adhesions were observed in the Ankaferd Blood Stopper group. Dissection of these epidural adhesions was difficult and accompanied by bleeding and disruption of the dura mater. CONCLUSION: The results of this study showed that there was no positive effect of Ankaferd Blood Stopper on the prevention of epidural fibrosis, which is one of the most significant problems following spinal surgery, and the epidural fibrosis actually increased.

The Effect of l-Arginine on Dural Healing After Experimentally Induced Dural Defect in a Rat Model.

BACKGROUND: Incomplete repair of the dura mater may result in numerous complications such as cerebrospinal fluid leakage and meningitis. For this reason, accurate repair of the dura mater is essential. In this study, the effect of systemic and local supplementation of l-arginine on dural healing was evaluated. METHODS: Thirty male Wistar rats were used and divided into control, local, and systemic l-arginine groups, with 10 rats in each. In each group, a 5-mm experimental incision was made at the lumbar segment of the dura mater and cerebrospinal fluid leakage was induced. Each group was divided into 2 subgroups and at the end of the first and sixth weeks, the rats were killed and the damaged segments of the dura were separated, histologically evaluated and the dural healing indicators including cell types, granulation tissue formation, collagen deposit, and vascularization were compared between groups. RESULTS: The systematic supplementation of l-arginine showed a significant effect in dural healing compared with the control group. After the first week, granulation formation increased considerably (P < 0.031), and after 6 weeks, collagen deposition and neovascularization were significantly different compared with the control group (P < 0.030; P < 0.009). In comparison between different groups at the end of the first and sixth weeks, maximum changes in healing indicators were observed in the systemic group and the least variations were related to the control group. CONCLUSIONS: The systemic supplementation of l-arginine may accelerate dural healing by increasing the level of granulation tissue formation, collagen deposition, and vascularization.

Inhibitory effect of high-frequency greater occipital nerve electrical stimulation on trigeminovascular nociceptive processing in rats.

Electrical stimulation of the greater occipital nerve (GON) has recently shown promise as an effective non-pharmacological prophylactic therapy for drug-resistant chronic primary headaches, but the neurobiological mechanisms underlying its anticephalgic action are not elucidated. Considering that the spinal trigeminal nucleus (STN) is a key segmental structure playing a prominent role in pathophysiology of headaches, in the present study we evaluated the effects of GON electrical stimulation on ongoing and evoked firing of the dura-sensitive STN neurons. The experiments were carried out on urethane/chloralose-anesthetized, paralyzed and artificially ventilated male Wistar rats. Extracellular recordings were made from 11 neurons within the caudal part of the STN that received convergent input from the ipsilateral facial cutaneous receptive fields, dura mater and GON. In each experiment, five various combinations of the GON stimulation frequency (50, 75, 100 Hz) and intensity (1, 3, 6 V) were tested successively in 10 min interval. At all parameter sets, preconditioning GON stimulation (250 ms train of pulses applied before each recording) produced suppression of both the ongoing activity of the STN neurons and their responses to electrical stimulation of the dura mater. The inhibitory effect depended mostly on the GON stimulation intensity, being maximally pronounced when a stimulus of 6 V was applied. Thus, the GON stimulation-induced inhibition of trigeminovascular nociceptive processing at the level of STN has been demonstrated for the first time. The data obtained can contribute to a deeper understanding of neurophysiological mechanisms underlying the therapeutic efficacy of GON stimulation in primary headaches.

Evaluation of the Biocompatibility of Polypyrrole Implanted Subdurally in GAERS.

This blinded controlled prospective randomized study investigates the biocompatibility of polypyrrole (PPy) polymer that will be used for intracranial triggered release of anti-epileptic drugs (AEDs). Three by three millimeters PPy are implanted subdurally in six adult female genetic absence epilepsy rats from Strasbourg. Each rat has a polymer implanted on one side of the cortex and a sham craniotomy performed on the other side. After a period of seven weeks, rats are euthanized and parallel series of coronal sections are cut throughout the implant site. Four series of 15 sections are histological (hematoxylin and eosin) and immunohistochemically (neuron-specific nuclear protein, glial fibrillary acidic protein, and anti-CD68 antibody) stained and evaluated by three investigators. The results show that implanted PPy mats do not induce obvious inflammation, trauma, gliosis, and neuronal toxicity. Therefore the authors conclude the PPy used offer good histocompatibility with central nervous system cells and that PPy sheets can be used as intracranial, AED delivery implant.

Acute and chronic triptan exposure neither alters rodent cerebral blood flow nor worsens ischemic brain injury.

Although it is still debated whether vasoconstriction underlies migraine resolution by triptans, they are not recommended in patients at cardiovascular risk. However, relationship between stroke incidence and triptan use is unclear, and it is unknown whether acute or chronic use of these drugs worsens ischemic brain injury. To address this issue, we investigated the effect of clinically-relevant doses of the potent cerebral artery vasoconstrictor eletriptan on cerebral blood flow (CBF) and brain infarct volumes, as well as on expression of genes involved in cerebrovascular regulation. We report that acute treatment of rats or mice with eletriptan did not reduce basal CBF, which promptly dropped upon treatment with prazosin or dihydroergotamine. Acute of chronic (1month) eletriptan also did not affect CBF changes and infarct volumes in mice undergoing brain ischemia/reperfusion. Finally, chronic eletriptan reduced brain mRNAs for PACAP and VIP, leaving unaffected those for 5HT1B/DR and CGRP. No significant transcript changes were found in dura mater. Data suggest that the impact of triptans on cerebral hemodynamic should be re-evaluated, as well as their propensity to increase stroke risk in migraineurs.

Five-Year Follow-Up of Bilateral Epidural Prefrontal Cortical Stimulation for Treatment-Resistant Depression.

BACKGROUND: Epidural prefrontal cortical stimulation (EpCS) represents a novel therapeutic approach with many unique benefits that can be used for treatment-resistant depression (TRD). OBJECTIVE: To examine the long-term safety and efficacy of EpCS of the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) for treatment of TRD. METHODS: Adults (N = 5) who were 21-80 years old with severe TRD [failure to respond to adequate courses of at least 4 antidepressant medications, psychotherapy and ≥20 on the Hamilton Rating Scale for Depression (HRSD24)] were recruited. Participants were implanted with bilateral EpCS over the FPC and DLPFC and received constant, chronic stimulation throughout the five years with Medtronic IPGs. They were followed for 5 years (2/1/2008-10/14/2013). Efficacy of EpCS was assessed with the HRSD24 in an open-label design as the primary outcome measure at five years. RESULTS: All 5 patients continued to tolerate the therapy. The mean improvements from pre-implant baseline on the HRSD24 were [7 months] 54.9% (±37.7), [1 year] 41.2% (±36.6), [2 years] 53.8% (±21.7), and [5 years] 45% (±47). Three of 5 (60%) subjects continued to be in remission at 5 years. There were 5 serious adverse events: 1 electrode 'paddle' infection and 4 device malfunctions, all resulting in suicidal ideation and/or hospitalization. CONCLUSION: These results suggest that chronic bilateral EpCS over the FPC and DLPFC is a promising and potentially durable new technology for treating TRD, both acutely and over 5 years.

The effect of vancomycin powder on human dural fibroblast culture and its implications for dural repair during spine surgery.

OBJECTIVE Surgical site infections (SSIs) are a major source of morbidity after spinal surgery. Several recent studies have described the finding that applying vancomycin powder to the surgical bed may reduce the incidence of SSI. However, applying vancomycin in high concentrations has been shown in vitro to inhibit osteoblast proliferation and to induce cell death. Vancomycin may have a deleterious effect on dural healing after repair of an intentional or unintentional durotomy. This study was therefore undertaken to assess the effect of different concentrations of vancomycin on a human dura mater cell culture. METHODS Human dura intended for disposal after decompressive craniectomy was harvested. Explant primary cultures and subcultures were subsequently performed. Cells were characterized through common staining and immunohistochemistry. A growth curve was performed to assess the effect of different concentrations of vancomycin (40, 400, and 4000 µg/ml) on cell count. The effect of vancomycin on cellular shape, intercellular arrangement, and viability was also evaluated. RESULTS All dural tissue samples successfully developed into fusiform cells, demonstrating pseudopod projections and spindle formation. The cells demonstrated vimentin positivity and also had typical features of fibroblasts. When applied to the cultures, the highest dose of vancomycin induced generalized cell death within 24 hours. The mean (± SD) cell counts for control, 40, 400, and 4000 µg/ml were 38.72 ± 15.93, 36.28 ± 22.87, 19.48 ± 6.53, and 4.07 ± 9.66, respectively (p < 0.0001, ANOVA). Compared with controls, vancomycin-exposed cells histologically demonstrated a smaller cytoplasm and decreased pseudopodia formation resulting in the inhibition of normal spindle intercellular arrangement. CONCLUSIONS When vancomycin powder is applied locally, dural cells are exposed to a concentration several times greater than when delivered systemically. In this in vitro model, vancomycin induced dural cell death, inhibited growth, and altered cellular morphology in a concentration-dependent fashion. Defining a safe vancomycin concentration that is both bactericidal and also does not inhibit normal dural healing is necessary.

Complications of Spinal Cord Stimulation and Peripheral Nerve Stimulation Techniques: A Review of the Literature.

OBJECTIVE: Spinal cord and peripheral neurostimulation techniques have been practiced since 1967 for the relief of pain, and some techniques are also used for improvement in organ function. Neuromodulation has recognized complications, although very rarely do these cause long-term morbidity. The aim of this article is to present a review of complications observed in patients treated with neurostimulation techniques. METHODS: A review of the major recent publications in the literature on the subjects of spinal cord, occipital, sacral, and peripheral nerve field stimulation was conducted. RESULTS: The incidence of complications reported varies from 30% to 40% of patients affected by one or more complications. Adverse events can be subdivided into hardware-related complications and biological complications. The commonest hardware-related complication is lead migration. Other lead related complications such as failure or fracture have also been reported. Common biological complications include infection and pain over the implant. Serious biological complications such as dural puncture headache and neurological damage are rarely observed. CONCLUSIONS: Spinal cord and peripheral neurostimulation techniques are safe and reversible therapies. Hardware-related complications are more commonly observed than biological complications. Serious adverse events such as neurological damage are rare.

Intraforaminal ozone therapy and particular side effects: preliminary results and early warning.

BACKGROUND: The term "low back pain syndrome" represents a complex nosological entity. The therapeutic approach is often only symptomatic and not etiologic. METHODS: Since 2013, 186 patients (97 males and 89 females, mean age 59.8 years) have undergone microsurgery for lumbar disc hernia or lumbar segmental stenosis. Among these patients, 23 had been previously treated with ozone therapy by the intraforaminal approach and 28 by intraforaminal steroid injections in other hospitals between 12 and 24 months before our clinical evaluation. These patients received 16 applications in an 8-week period (standard therapy). RESULTS: During the surgery, many hard adhesions between the soft tissues and bony structures were unexpectedly discovered. In particular, it was noted that the root contracted and had firm adhesions to the dural sac and/or fragmented disc, which were difficult to resolve. These specific pathological patterns were observed only in the patients who received ozone injections by the intraforaminal approach. We did not find any pathological abnormalities in the patients who did not receive any injections or who received intraforaminal steroid injections. Thus, we could exclude that the tissue damage was due to the mechanical action of the needle. CONCLUSION: It is important to assert that ozone therapy procedures can be associated with several major complications. Therefore, performing a revision of the guidelines and protocols for ozone therapy application is indispensable.

Efficacy of topical cross-linked hyaluronic acid hydrogel in preventing post laminectomy/laminotomy fibrosis in a rat model.

Post-laminectomy/laminotomy epidural fibrosis (EF) has been implicated as an important cause of failed back syndrome (FBS). The various clinical approaches used to control EF yield mixed outcomes. Cross-linked hyaluronic acid hydrogel (cHA) was synthesized to increase mechanical stability and residence time. We evaluated the therapeutic attenuation of proliferative EF in laminectomy/laminotomy groups treated and not treated with cHA. A bilateral T11-L1 total laminectomy or unilateral T12 laminotomy was done on four groups (n = 10 each) of Sprague-Dawley rats and then histologically examined 2 months post-surgery: (I) laminectomy group treated with and (II) not treated with cHA, (III) laminotomy group treated with and (IV) not treated with cHA. The grade of EF, the diameters within the spinal canal, dura mater thickness, and the area of the epidural space, subarachnoid space, and conus medullaris space were assessed. The cHA-treated subgroups (I, III) had a significantly lower grade of EF, thinner dura mater, and larger epidural and subarachnoid spaces than did the control subgroups (II, IV) (p < 0.05). The cHA formed a solid interpositional membrane barrier that prevented invasive fibrosis, and also helped reduce pathological changes to the adjacent structures. In conclusion, topically applied cHA is effective for reducing EF.

Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage.

BACKGROUND: Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. METHODS: In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface. Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [(51)Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum. RESULTS: We observed that [(51)Cr]-EDTA did not pass into the central nervous system (CNS) in a major way. However, [(51)Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants. CONCLUSIONS: With these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG is readily exposed to circulating molecules. The TG could provide a site of anti-migraine drug interaction with effect on the trigeminal system.