Dehydroepiandrosterone Sulfate Is Neuroprotective when Administered Either before or after Injury in a Focal Cortical Cold Lesion Model

Dehydroepiandrosterone and its sulfate (DHEAS) are sex hormone precursors that exert marked neurotrophic and/or neuroprotective activity in the central nervous system. The present study evaluated the effects of DHEAS and 17β-estradiol (E2) in a focal cortical cold lesion model, in which DHEAS (50 mg/kg, sc) and E2 (35 mg/kg, sc) were administered either as pretreatment (two subsequent injections 1 d and 1 h before lesion induction) or posttreatment (immediately after lesion induction). The focal cortical cold lesion was induced in the primary motor cortex by means of a cooled copper cylinder placed directly onto the cortical surface. One hour later, the animals were killed, the brains cut into 0.4-mm-thick slices, and the sections stained with 1% triphenyltetrazolium chloride. The volume of the hemispheric lesion was calculated for each animal. The results demonstrated that the lesion area was significantly attenuated in both the DHEAS- and E2- pre- and posttreated groups and that in the presence of letrozole, a nonsteroidal aromatase inhibitor, no neuroprotection was observed, suggesting that the beneficial effect of DHEAS on the cold injury might depend on the conversion of DHEAS to E2 within the brain. It is concluded that even a single posttraumatic administration of DHEAS may be of substantial therapeutic benefit in the treatment of focal brain injury with vasogenic edema.

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Assessment of acute and sub-chronic neurotoxicity of Morus alba L. fruits in rodents

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-020-00110-5 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Arpita Paul ◽

Anshul Shakya ◽

Md Kamaruz Zaman

Keyword(s):

Central Nervous System ◽

Morus Alba ◽

Neuroprotective Activity ◽

Repeated Treatment ◽

Fruit Extract ◽

Hot Plate ◽

Organ Weights ◽

Behavioural Responses ◽

Limit Test ◽

The Central Nervous System

Abstract Background Morus alba L. fruits are consumed since long for their nutritional and medicinal values. Although there were studies on the neuroprotective activity of the fruit extract, safety profile of the fruit extract is not yet explored as per the recommended standard guidelines over the central nervous system (CNS). The present work was aimed to assess the neurotoxicity profile of chemically characterized extract of M. alba L. fruits (MA) using validated OECD guidelines, i.e., 425 and 424 in rodents. Results Neurobehavioural parameters were examined for motor, sensory and behavioural responses using actophotometer, hot plate and light and dark box test, respectively as per OECD 424. Interestingly, no sign of mortality and/or adversity on mice treated per-orally with MA (2000 mg/kg) was observed during the limit test as per OECD 425. Further, rats treated with MA (1000, 300 and 100 mg/kg, p.o.) for 28 days, showed insignificant (p < 0.05) changes in body weight, food consumption, neurobehavioural responses, organ weights and biochemical, haematological and histopathological features when compared with vehicle-treated animals. Conclusion The outcome of findings suggests that MA is safe in acute oral as well as sub-chronic (28 days) administration in mice and rats respectively. MA (1000 mg/kg) did not pose any toxic sign and symptoms on neurobehavioural responses in rats even after 28 days repeated treatment in compliance with OECD 424.

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Multifocal glioblastoma multiform with “encephalitis-like presentation” : a case report

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-021-00407-2 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Issam Sa’adeh ◽

Mohamed Jamal Saadh

Keyword(s):

Vasogenic Edema ◽

Neurological Deficits ◽

Herpes Simplex Virus 1 ◽

Glioblastoma Multiform ◽

Atypical Clinical Presentation ◽

Mri Scans ◽

The Central Nervous System ◽

Magnetic Resonance Imaging Mri ◽

Simplex Virus ◽

Multifocal Glioblastoma

Abstract Background Glioblastoma multiform is the most common and aggressive type of primary malignant tumor that affects the central nervous system in adults. It clinically presents with seizures, headache, and/or progressive focal neurological deficits. Radiologically, glioblastoma multiform appears as a single distinguishable, large heterogeneous lesion affecting the cerebrum with characteristic central necrosis, marginal enhancement, and surrounding vasogenic edema. This article describes a patient that exhibited an atypical clinical presentation of multifocal glioblastoma multiform with misleading early radiological features that simulated herpetic encephalitis. Results A 66-year-old female that presented with left-sided hemiparesis and left partial motor seizures underwent multi-slice computed tomography (MSCT) and magnetic resonance imaging (MRI) scans. A cerebrospinal fluid (CSF) polymerase chain reaction (PCR) test was also performed to screen for herpes simplex virus 1 (HSV-1). Conclusions The early stages of glioblastoma may manifest as symptoms typical to encephalitis, which can delay diagnosis and treatment. Therefore, early diagnosis and identification of atypical glioblastoma multiform presentations, as reported in this article, are essential.

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The kallikrein-kinin system as mediator in vasogenic brain edema

Journal of Neurosurgery ◽

10.3171/jns.1986.64.2.0269 ◽

1986 ◽

Vol 64 (2) ◽

pp. 269-276 ◽

Cited By ~ 85

Author(s):

Andreas Unterberg ◽

Claudia Dautermann ◽

Alexander Baethmann ◽

Werner Müller-Esterl

Keyword(s):

Brain Edema ◽

Vasogenic Edema ◽

Specific Inhibition ◽

Kinin System ◽

Content Type ◽

Cold Lesion ◽

Highly Active ◽

Mediator Role ◽

Kallikrein Kinin System ◽

The Brain

✓ Evidence has previously been provided that administration of kinins to the cerebrum causes edema and opening of the blood-brain barrier. It has further been shown that these highly active compounds are formed in the brain under pathophysiological conditions. Their formation was enhanced when cerebral blood flow became compromised by an increase in intracranial pressure. Final evidence, however, was not available as to whether specific inhibition of the kallikrein-kinin (KK) system has a therapeutic function in acute head injury. The authors have demonstrated in rabbits that inhibition of the activating enzyme kallikrein by aprotinin or by aprotinin plus soybean trypsin inhibitor (SBTI), which interfere with plasma and tissue kallikrein, is associated with a decrease in formation of posttraumatic swelling after a standardized cold lesion to the brain. Saline-treated control animals with cerebral cold-induced injury had an increase in hemispheric weight 24 hours later of 13.0% ± 0.8% (standard error of the mean) in the damaged hemisphere compared to the contralateral nondamaged hemisphere. Administration of aprotinin or aprotinin plus SBTI led to a significant reduction of hemispheric swelling of 10.1% ± 0.7% or 10.4% ± 0.7%, respectively. In animals receiving SBTI only, hemispheric swelling evolving from cold injury was not significantly reduced. Therapeutic reduction of brain edema by aprotinin cannot be attributed to a nonspecific effect on the blood pressure, which in the experimental groups remained almost normal as compared to the control animals. Failure of SBTI to influence posttraumatic brain swelling may have resulted from disturbances in intravascular coagulation. Measurements of aprotinin in plasma and tissue demonstrate that the inhibitor doses employed are within an effective therapeutic range. Attenuation of brain edema by specific inhibition of the KK system provides evidence for a mediator role of kinins in vasogenic edema. Clinical trials with inhibitors of the KK system in acute forms of traumatic lesions associated with vasogenic edema appear worthwhile.

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Sarcoidosis Presenting as an Intramedullary Spinal Cord Lesion

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100052884 ◽

2001 ◽

Vol 28 (2) ◽

pp. 163-166 ◽

Cited By ~ 10

Author(s):

F.B. Maroun ◽

F.J. O'Dea ◽

G. Mathieson ◽

G. Fox ◽

G. Murray ◽

...

Keyword(s):

Respiratory Distress ◽

Therapeutic Benefit ◽

Acute Onset ◽

Respiratory Compromise ◽

Intramedullary Spinal Cord ◽

Respiratory Involvement ◽

Meige Syndrome ◽

Anoxic Event ◽

Focal Brain Injury ◽

The Relationship

ABSTRACT:Objectives:Meige syndrome is a movement disorder that includes blepharospasm and oromandibular dystonias. Its etiology may be idiopathic (primary) or it may arise secondary to focal brain injury. Acute respiratory distress as a feature of such dystonias occurs infrequently. A review of the literature on Meige syndrome and the relationship between dystonias and respiratory compromise is presented.Methods:A 60-year-old woman suffered a cerebral anoxic event secondary to manual strangulation. She developed progressive blepharospasm combined with oromandibular and cervical dystonias. Neuroimaging demonstrated bilateral damage localized to the globus pallidus. Years later, she presented to the emergency department in intermittent respiratory distress associated with facial and cervical muscle spasms.Results and conclusions:Increasing frequency and severity of the disorder was noted over years. The acute onset of respiratory involvement required intubation and eventual tracheotomy. A partial therapeutic benefit of tetrabenazine was demonstrated.

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Role of the Ipsilateral Motor Cortex in Voluntary Movement

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100032947 ◽

1997 ◽

Vol 24 (04) ◽

pp. 284-291 ◽

Cited By ~ 92

Author(s):

Robert Chen ◽

Leonardo G. Cohen ◽

Mark Hallett

Keyword(s):

Motor Cortex ◽

Functional Recovery ◽

Voluntary Movement ◽

Primary Motor Cortex ◽

Repetitive Transcranial Magnetic Stimulation ◽

Normal Subjects ◽

Older Children ◽

Focal Brain Injury ◽

Complex Sequences ◽

The Right

ABSTRACT:The ipsilateral primary motor cortex (M1) plays a role in voluntary movement. In our studies, we used repetitive transcranial magnetic stimulation (rTMS) to study the effects of transient disruption of the ipsilateral M1 on the performance of finger sequences in right-handed normal subjects. Stimulation of the M1 ipsilateral to the movement induced timing errors in both simple and complex sequences performed with either hand, but with complex sequences, the effects were more pronounced with the left-sided stimulation. Recent studies in both animals and humans have confirmed the traditional view that ipsilateral projections from M1 to the upper limb are mainly directed to truncal and proximal muscles, with little evidence for direct connections to distal muscles. The ipsilateral motor pathway appears to be an important mechanism for functional recovery after focal brain injury during infancy, but its role in functional recovery for older children and adults has not yet been clearly demonstrated. There is increasing evidence from studies using different methodologies such as rTMS, functional imaging and movement-related cortical potentials, that M1 is involved in ipsilateral hand movements, with greater involvement in more complex tasks and the left hemisphere playing a greater role than the right.

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Stimulatory Adrenocortical Effects of a Selective Estrogen Receptor Modulator in Ovariectomized Female Macaques

Toxicologic Pathology ◽

10.1177/0192623311425509 ◽

2011 ◽

Vol 40 (1) ◽

pp. 55-61 ◽

Cited By ~ 3

Author(s):

Charles E. Wood ◽

Ronda C. Stavisky ◽

Jette Nowak ◽

Jay R. Kaplan

Keyword(s):

Estrogen Receptor ◽

Macaca Fascicularis ◽

Dehydroepiandrosterone Sulfate ◽

Selective Estrogen Receptor Modulator ◽

Adrenocortical Function ◽

Target Dose ◽

Treatment Groups ◽

Receptor Modulator ◽

17Β Estradiol

Here, we report the effects of estrogen and the selective estrogen receptor modulator (SERM) levormeloxifene on adrenocortical measures in ovariectomized female cynomolgus monkeys ( Macaca fascicularis). Animals were randomized into one of five treatment groups, each containing 23 to 26 animals: (1) placebo, (2) 0.016 mg/kg 17β-estradiol (E2), (3) 0.5 mg/kg levormeloxifene (L1), (4) 1.0 mg/kg levormeloxifene (L2), and (5) 5.0 mg/kg levormeloxifene (L3). Treatments were administered orally each day for 18 mo. All doses of levormeloxifene resulted in adrenal weights at least 50% greater than placebo ( p < .0001 for all). The target dose of levormeloxifene (L2) resulted in higher serum concentrations of cortisol (+63%), dehydroepiandrosterone-sulfate (+73%), and androstenedione (+37%) compared with the placebo group ( p < .05 for all). In contrast, E2 resulted in no significant differences in adrenal weight or adrenocortical steroids. Oral E2 and all SERM doses resulted in similar reductions in serum gonadotropins and at least threefold greater uterine weight versus placebo ( p < .0001 for all). Results indicate that the SERM levormeloxifene, in contrast to E2, may have robust stimulatory effects on adrenocortical hormones in a postmenopausal model. These findings warrant further investigation into long-term SERM effects on adrenocortical function.

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Bioenergetics of acute vasogenic edema

Journal of Neurosurgery ◽

10.3171/jns.1980.53.4.0470 ◽

1980 ◽

Vol 53 (4) ◽

pp. 470-476 ◽

Cited By ~ 19

Author(s):

Leslie N. Sutton ◽

Frank Welsh ◽

Derek A. Bruce

Keyword(s):

White Matter ◽

Adenosine Triphosphate ◽

Vasogenic Edema ◽

Lactate Concentration ◽

High Energy ◽

High Energy Phosphates ◽

High Energy Phosphate ◽

Content Type ◽

Cold Lesion ◽

Fine Print

✓ The bioenergetic mechanisms of vasogenic edema were studied by measuring concentrations of adenosine triphosphate (ATP), phosphocreatine (CrP), and lactate in rapidly frozen edematous white matter in cats. When edema was produced using a cold lesion, it was found that both ATP and CrP were reduced to one-half of control values, and that lactate was elevated. When a correction was applied for dilution, however, it was found that high-energy phosphates were equal to control values, and that lactate was even more significantly elevated. This pattern contrasted with that seen in white-matter ischemia, in which CrP is depressed out of proportion to ATP. Finally, it was found that the white-matter lactate concentration in the plasma infusion model of edema was increased. It is concluded that vasogenic edema induces an increase in lactate, but does not deplete high-energy phosphate compounds in affected white matter.

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The effects of cold-induced brain edema and white-matter ischemia on the somatosensory evoked response

Journal of Neurosurgery ◽

10.3171/jns.1980.53.2.0180 ◽

1980 ◽

Vol 53 (2) ◽

pp. 180-184 ◽

Cited By ~ 18

Author(s):

Leslie N. Sutton ◽

Derek A. Bruce ◽

Frank Welsh

Keyword(s):

White Matter ◽

Brain Edema ◽

Vasogenic Edema ◽

Evoked Response ◽

Content Type ◽

Cold Lesion ◽

Somatosensory Evoked Response ◽

Electrophysiological Effects ◽

Fine Print ◽

Cortical Waves

✓ The electrophysiological effects of cold-lesion edema and white-matter ischemia were studied in cats by reference to the short-latency somatosensory evoked response. The primary cortical waves were found to be considerably delayed following a period of white-matter ischemia; however, cold-lesion edema appeared to have no significant effect on the evoked response. The authors conclude that vasogenic edema does not interfere with axonal functioning by an ischemic mechanism.

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