Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of progesterone, its A-ring-reduced metabolites, allopregnanolone, tetrahydroxydeoxycorticosterone and the synthetic neuroactive steroid alphaxalone were evaluated in a rat model of plasma extravasation within the meninges following unilateral electrical stimulation (ES) of the trigeminal ganglion (0.6 mA, 5 ms, 5 min) or substance P administration (1 nmol kg-1, i.v.). 2. When administered 55 min prior to electrical stimulation, progesterone (> or = 500 micrograms, s.c.) dose-dependently decreased plasma extravasation within the meninges (ED50: 650 micrograms) but not within conjunctiva and tongue. Promegestone (R5020), a non-metabolized progesterone agonist (1000 micrograms, i.p.) was ineffective. The administration of progestrone (> or = 500 micrograms s.c.) 55 min prior to substance P partially suppressed plasma extravasation within the meninges (ED50: 550 micrograms). 3. The GABAA-antagonist, bicuculline (ED50: 8.2 micrograms kg-1, i.p.) but not the GABAB-antagonist, phaclofen (100 micrograms kg-1, i.p.) attenuated the effects of progesterone after electrical stimulation and substance P administration. 4. The metabolites of progesterone, allopregnanolone (3 alpha-hydroxy-5 alpha- pregnan-20-one (THP); ED50: 0.58 micrograms kg-1, i.p.), tetrahydroxydeoxycorticosterone (3 alpha,21- dihydroxy-5 alpha-pregnan-20-one (THDOC); ED50: 1.2 micrograms kg-1, i.p.) as well as the synthetic steroid alphaxalone (3 alpha-hydroxy-5 alpha-pregnane-11,20-dione; ED50: 1.8 micrograms kg-1, i.p.) suppressed plasma extravasation dose-dependently following ES, whereas the epimer of allopregnanolone, 3 beta-hydroxy-5 alpha-pregnan-20-one (100 micrograms kg-1, i.p.), did not. Extravasation caused by SP administration was partially suppressed by allopregnanolone (> or = 1 microgram kg-1, i.p.) (ED50: 2.1 micrograms kg-1). 5. The effect of progesterone (1000 micrograms, s.c.) and allopregnanolone (100 micrograms kg-1, i.p.) on neurogenic plasma extravasation was reversed by bicuculline (10 micrograms kg-1, i.p.) or by a congener, bicuculline-methiodide (10 micrograms kg-1, i.p.) which does not cross the blood brain barrier. 6. Progesterone (1000 micrograms, s.c.) had no effect on mean arterial blood pressure or heart rate when measured for 60 min after administration. 7. These results indicate that neurosteroid modulation of a GABAA-receptor located outside the blood brain barrier suppresses neurogenic and substance P-induced plasma extravasation within the meninges. The findings are consistent with previously reported data showing that valproic acid and muscimol inhibit meningeal oedema by bicuculline-sensitive mechanisms. Drugs which activate GABAA-receptors and its modulatory sites might be clinically effective in the treatment of migraine and cluster headache.
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PMID:GABAA-receptor-mediated effects of progesterone, its ring-A-reduced metabolites and synthetic neuroactive steroids on neurogenic oedema in the rat meninges. 882 49

For many decades, headache and migraine were though to evolve from dilated cranial blood vessels. Vasoconstrictors such as ergotamine and, more recently, sumatriptan were considered appropriate treatments. With the introduction of animal models and the emergence of molecular pharmacology, this traditional concept has been challenged, and an important role for neuropeptides, neuronal receptors and neurogenic inflammation is emerging. Neurogenic inflammation develops within the meninges as a consequence of neuropeptide release from primary afferent fibers and has been hypothesized to be of important in migraine. Neurogenic inflammation provides protection for many organs, contributes to tissue repair and serves as a useful model to define the receptor population and peptide mechanisms of relevance to drug discovery in migraine. The possible role played by neurotransmitters and neuropeptides in migraine and their receptors as potential targets for treatment will be discussed.
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PMID:Neurotransmitters and neuropeptides in headache. 883 12

A case of cerebral aspergillosis during induction chemotherapy for acute lymphoblastic leukemia was described. A 5-year-old boy complained of headache and left homonymous hemianopsia during induction chemotherapy for acute lymphoblastic leukemia. CT scan and MR imaging survey demonstrated cerebral fungal lesion as well as multifocal lung lesions. A cerebral lesion appeared as a low density mass in right occipital lobe with marginal enhancement on CT scan, and iso- and high-signal intensity appeared with marginal gadolinium enhancement on T1- and T2-weighted MR imaging. Although fungus balls in the lung responded well to daily intravenous administration of amphotericin-B for 2 months, the cerebral lesion showed a rather expansive character as invading into neighbouring falx, opposite occipital lobe, meninges, and occipital bone. Extensive removal of the brain lesion from the parenchyma, falx, invaded dura, and skull was surgically performed. The lesion was confirmed as aspergillosis by Grocott's methenamine histological stain. Surgical intervention and concomitant use of amphotericin-B for a month resulted in complete remission of the aspergillosis. After 6 years, a cranioplasty was successfully completed for the occipital bone defect.
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PMID:[A case of cerebral aspergillosis associated with induction chemotherapy for acute lymphoblastic leukemia]. 895 97

The headaches that accompany certain intracranial pathologies (such as meningitis, subarachnoid haemorrhage and tumour) have been considered to result from mechanical or chemical stimulation of pain-sensitive structures of the intracranial meninges. Although the recurrent headache of migraine is of unknown origin and is not accompanied by an identifiable pathology, it shares with intracranial headaches features that suggest an exaggerated intracranial mechanosensitivity (worsening of the pain by coughing, breath-holding or sudden head movement). One possible basis for such symptoms would be a sensitization of meningeal afferents to mechanical stimuli. Previous studies of neuronal responses to meningeal stimulation have focused primarily on cells in the central portion of the trigeminal pathway, and have not investigated the possible occurrence of sensitization. We have recorded the activity of primary afferent neurons in the rat trigeminal ganglion that innervate the dural venous sinuses. Chemical stimulation of their dural receptive fields with inflammatory mediators both directly excited the neurons and enhanced their mechanical sensitivity, such that they were strongly activated by mechanical stimuli that initially had evoked little or no response. These properties of meningeal afferents (chemosensitivity and sensitization) may contribute to the intracranial mechanical hypersensitivity that is characteristic of some types of clinically occurring headaches, and may also contribute to the throbbing pain of migraine.
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PMID:Sensitization of meningeal sensory neurons and the origin of headaches. 895 68

Gamma-aminobutyric acid (GABA) receptors are ubiquitous inhibitory receptors in the central and peripheral nervous systems. Valproic acid (2-propylpentanoic acid), which enhances GABA synthesis and blocks degradation, is useful in migraine treatment and may act through activation of GABA receptors to modulate trigeminal nociceptive neurons innervating the meninges. To investigate this possibility, we tested the effect of valproate and allopregnanolone, a metabolite of progesterone, which binds and modulates the GABA receptor in an animal model of cephalic pain. One hundred ten Hartley guinea pigs were pretreated with either valproate or allopregnanolone 30 minutes prior to activation of trigeminal afferent fibers via intracisternal injection of the irritant, capsaicin. The effects of valproic acid and allopregnanolone were examined on c-fos expression within the trigeminal nucleus caudalis (lamina I, II), the termination site for small unmyelinated C fibers projecting from the meninges. C-fos positive cells were counted at three representative levels (rostral, middle, and caudal) by an observer naive to the treatment group. We found that valproate (> or = 10 mg/kg, IP) reduced labeled cells by 52% (P < 0.05) and allopregnanolone (> or = 100 mg/kg, IP) reduced labeled cells by 42% (P < 0.01). Bicuculline (GABAA antagonist), but not phaclofen (GABAB antagonist), blocked the valproate effect, thereby documenting the importance of GABAA receptors. We conclude that the attenuation of c-fos-LI by valproate and allopregnanolone is mediated via GABAA receptors. These studies complement prior experiments showing that valproic acid and allopregnanolone block neurogenic inflammation within the meninges via GABAA receptor-mediated mechanisms. The findings suggest a potential strategy for discovering new antimigraine drugs with high affinity for the GABAA receptor and its modulatory sites.
Headache
PMID:Wolff Award 1996. The actions of valproate and neurosteroids in a model of trigeminal pain. 899 May 96

Spontaneous intracranial hypotension is a rare but well known entity first described by the German neurosurgeon Schaltenbrand. We report the clinical and radiological findings of four patients (2 males, 2 females, mean age 55 years) presenting with this clinical entity and peculiar constant MRI findings. Intense postural headache was present in all patients together with a very low CSF pressure at lumbar tap although none of the patients had any history of recent lumbar puncture, spinal or cerebral surgery or cranio-cervical trauma. MRI revealed in all patients an intense meningeal enhancement and thickening which was most prominent on the dural side of the subdural space. The ventricular system was thin, presenting almost like slit ventricules. A downward shift of the cerebellar tonsils and hemorrhagic subdural collections were also observed in two patients. Biopsy of meninges performed in two patients showed fibrosis of the leptomeninges together with signs of old hemorrhage in one case. We postulate that histologic and radiologic changes are due to chronic subdural bleeding in relation with abnormal displacement of the nervous structures due to intracranial hypotension. The underlying cause of spontaneous intracranial hypotension is rarely established and the course of the disease is benign. Some authors have advocated to perform isotopic cysternography in search for a CSF leak, particularly in the spine, that could be surgically corrected. No such investigation has been conducted yet in our patients because the spontaneous evolution has been mostly favorable.
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PMID:[Spontaneous intracranial hypotension syndrome]. 903 53

We report a unique case of histologically confirmed meningeal fibrosis in a child who had progressive ischemic neurologic symptoms before the delayed diagnosis of an intracranial primitive neuroectodermal tumor (PNET) was made > 1 year after initial presentation. This pathology has previously been described after neurosurgical procedures, subarachnoid hemorrhage, cranial irradiation, and with no known etiology, but has never been reported in association with a central nervous system neoplasm. In a 6-year-old boy with headaches of several months' duration MRI demonstrated hydrocephalus, a right cerebellopontine angle cyst, and dural enhancement. Biopsies of the thickened meninges taken when the cyst was surgically fenestrated demonstrated only fibrosis with no evidence of infection, hemorrhage, or neoplasm. In the next 6 months, the child had two acute stroke-like episodes with alternating hemiparesis that gradually improved. There were ischemic changes in the diencephalon on MRI. Repeat dural biopsies were unchanged. One year after the initial operation, a left hemiparesis recurred and MRI demonstrated multiple intracranial masses in the cerebral cortex, cerebellum, suprasellar area, and cauda equina. After surgical resection, the cortical mass was found to be a PNET. All the lesions regressed after treatment with radiation and chemotherapy. We hypothesize that the meningeal fibrosis represented a "desmoplastic" reaction to an occult PNET, similar to the fibrous proliferation with cerebellar desmoplastic medulloblastoma except for the extent of the meningeal involvement and the long undetected parenchymal tumor. The mechanism of the ischemic brain injury was most likely vascular involvement by the fibrotic process, either directly or by predisposition to vasoconstriction.
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PMID:Leptomeningeal fibrosis and the delayed diagnosis of a central nervous system neoplasm (primitive neuroectodermal tumor). 904 9

A rare case of tuberculous meningitis (TBM) causing unilateral thickening of meninges, is described here. The 50 year old male is presented with hemicranial headache and unilateral multiple cranial nerve involvement without any long tract signs. Magnetic resonance imaging (MRI) scan including enhanced studies showed a hemicranial thickening of the meninges. Biopsy of the meninges revealed tuberculosis. The patient improved gradually on antitubercular treatment (ATT). Follow-up at 6 months revealed significant improvement in neurological status. Though tuberculous involvement of the central nervous system (CNS) is very common in India, hemicranial meningeal involvement has never been reported.
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PMID:Unilateral meningeal thickening: a rare presentation of tuberculous meningitis. 910 71

Production of prostaglandins is a critical step in transducing immune stimuli into central nervous system (CNS) responses, but the cellular source of prostaglandins responsible for CNS signalling is unknown. Cyclooxygenase catalyzes the rate-limiting step in the synthesis of prostaglandins and exists in two isoforms. Regulation of the inducible isoform, cyclooxygenase 2, is thought to play a key role in the brain's response to acute inflammatory stimuli. In this paper, we report that intravenous lipopolysaccharide (LPS or endotoxin) induces cyclooxygenase 2-like immunoreactivity in cells closely associated with brain blood vessels and in cells in the meninges. Neuronal staining was not noticeably altered or induced in any brain region by endotoxin challenge. Furthermore, many of the cells also were stained with a perivascular microglial/macrophage-specific antibody, indicating that intravenous LPS induces cyclooxygenase in perivascular microglia along blood vessels and in meningeal macrophages at the edge of the brain. These findings suggest that perivascular microglia and meningeal macrophages throughout the brain may be the cellular source of prostaglandins following systemic immune challenge. We hypothesize that distinct components of the CNS response to immune system activation may be mediated by prostaglandins produced at specific intracranial sites such as the preoptic area (altered sleep and thermoregulation), medulla (adrenal corticosteroid response), and cerebral cortex (headache and encephalopathy).
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PMID:Intravenous lipopolysaccharide induces cyclooxygenase 2-like immunoreactivity in rat brain perivascular microglia and meningeal macrophages. 913 Jun 63

Human monocytic ehrlichiosis is a recently described tick-borne infection with the rickettsial organism Ehrlichia chaffeensis. We describe a patient with documented E chaffeensis infection and multiple organ system involvement. Prominent neurologic symptoms and signs included severe headache, meningismus, and altered mental status. Additional neurologic findings included unilateral arm weakness and a Bell's palsy. Biopsy of brain and meninges demonstrated an infiltrate of atypical lymphoid cells in the leptomeninges with involvement of blood vessel walls and extension into the Virchow-Robin spaces. Bone marrow biopsy revealed fibrin-ringed granulomas. The patient also developed a nonspecific increase in immunoglobulin production. Host immune response may play a critical role in the pathophysiology of ehrlichiosis.
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PMID:A case of acute monocytic ehrlichiosis with prominent neurologic signs. 919 77


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