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Biomedical subjects

T K McIntosh

Publications and source records attributed to T K McIntosh.

212 records · Page 12Linked to original sources
PubMed1980

Effects of morphine, beta-endorphin and naloxone on catecholamine levels and sexual behavior in the male rat.

Intraperitoneal administration of the opiate antagonist naloxone hydrochloride (30 mg/kg) to sexually experienced male rats caused a significant reduction in mount and intromission latencies, number of mounts preceding ejaculation and ejaculation latencies. Intraperitoneal adminstration of naloxone (30 mg/kg) also stimulated persistant non-copulators to begin mating and to ejaculate within a twenty minute test period. Conversely, intraperitoneal administration of morphine sulphate (6 mg/kg) as well as intraventricular injection of the endogenous opiate beta-endorphin (6 micrograms) produced a complete loss of copulatory behavior in male rats. The deficit in sexual behavior induced by beta-endorphin was correlated with a significant increase in hypothalamic norepinephrine levels. It is suggested that the endogenous opiates may be involved in the mediation of sexual behavior via an interaction with central catecholaminergic systems.

Animals↗
PubMed1980

Circadian periodicity of plasma corticosterone levels in rats subjected to hemorrhagic shock and surgical trauma.

The effects of surgical trauma and hemorrhagic shock on the circadian rhythmicity of corticosteroid secretion in the rat were investigated. The estimations were performed at 4-hour intervals for a 24-hour period. Control animals exhibited a characteristic circadian rhythm of plasma corticosterone with peak concentrations occurring at 8 p.m. followed by a gradual fall during the night, reaching a minimum at 8 a.m. Severe stress induced by hemorrhagic shock or surgical trauma caused a dramatic alteration in corticosterone rhythms which persisted up to 72 h following surgery or hemorrhage. It is apparent that the physiological mechanisms which regulate adrenal rhythmicity are disrupted for a prolonged period following major stress or trauma.

Animals↗
PubMed1977

Excreted urine, bladder urine, and the delay of sexual maturation in female house mice.

A series of experiments tested effects of excreted and bladder urine of group- and singly-caged female house mice (Mus musculus) on sexual maturation of young female mice caged alone or in groups of eight. Puberty was determined by vaginal smears. A maturation-delaying pheromone was present in bladder urine of all female mice and excreted urine of group-caged females, but not in excreted urine from singly-caged females. Test mice treated with bladder urine homogenized with urethras from singly-caged females matured at the same age as controls. Apparently the urethras or associated glands of singly-caged females produce a substance which deactivates the maturation-delaying pheromone contained in bladder urine.

Animals↗
PubMedDate not supplied

Rational design of an animal model for Alzheimer's disease: introduction of multiple human genomic transgenes to reproduce AD pathology in a rodent.

A major obstacle to understanding the pathogenesis of Alzheimer's disease is the lack of easily studied animal models. Our approach is to apply transgenic methods to humanize mice and rats, employing methods that introduce large genomic transgenes, because this improves the level of transgene protein expression and the tissue specificity of expression. Our plan is to reproduce AD pathology in rodents by making them transgenic for several human proteins involved in AD. This report describes transgenic animal lines that we have produced, and summarizes our current approach and future plans. Two human genes known to be involved in AD pathology are the amyloid precursor protein (APP) and the E4 isoform of apolipoprotein E (apoE4). So far, we have produced and analyzed a transgenic line carrying the entire human APP gene cloned in a yeast artificial chromosome. We have also produced but not yet analyzed a mouse carrying the human apoE4 gene. Work is in progress to produce a transgenic line carrying a disease-causing mutation in the human APP gene. As we produce these animals, we are breeding them together, and also breeding them with a mouse line that lacks endogenous apoE, to produce an animal model carrying several human proteins whose interaction is believed to be instrumental in development of AD pathology. These transgenic animals will be useful for dissecting the biochemical and physiological steps leading to AD, and for development of therapies for disease intervention.

Alzheimer Disease↗
PubMedDate not supplied

Magnetization transfer imaging of diffuse axonal injury following experimental brain injury in the pig: characterization by magnetization transfer ratio with histopathologic correlation.

PURPOSE: Our goal was to evaluate the use of the magnetization transfer ratio (MTR) in the detection of diffuse axonal injury (DAI) resulting from traumatic brain injury in a swine model. METHOD: DAI was created by applying a nonimpact, coronal plane, rotational acceleration to the heads of miniature swine (n = 4). GE imaging was performed with and without off-resonance MT saturation. Histologic correlation of axonal injury with MRI was performed 7 days postinjury. Thirty-one subcortical white matter regions and 10 deep white matter regions were selected for the direct comparison of histologic data and MTR measurements. RESULTS: Nineteen of 41 examined locations exhibited histologic evidence of axonal injury. The mean MTR in regions with axonal damage was significantly less than in regions without axonal damage. These changes were observed both in regions demonstrating high signal intensity on T2-weighted images (T2WI) (p <0.0001, n = 6) and in regions with no signal intensity change on T2WI (p < 0.05, n = 13). CONCLUSION: These results suggest that the measurement of MTR may have the potential for evaluation axonal damage in DAI following traumatic brain injury even when conventional T2WI does not demonstrate the lesion.

Animals↗
PubMedDate not supplied

Mechanical characterization of an in vitro device designed to quantitatively injure living brain tissue.

Due to the nonlinear, viscoelastic material properties of brain, its mechanical response is dependent upon its total strain history. Therefore, a low strain rate, large strain will likely produce a tissue injury unique from that due to a high strain rate, moderate strain. Due to a lack of current understanding of specific in vivo physiological injury mechanisms, a priori assumptions cannot be made that a low strain rate injury induced by currently employed in vitro injury devices is representative of clinical, nonimpact, inertial head injuries. In the present study, an in vitro system capable of mechanically injuring cultured tissue at high strain rates was designed and characterized. The design of the device was based upon existing systems in which a clamped membrane, on which cells have been cultured, is deformed. However, the present system incorporates three substantial improvements: (1) noncontact measurement of the membrane deflection during injury; (2) precise and independent control over several characteristics of the deflection; and (3) generation of mechanical insults over a wide range of strains (up to 0.65) and strain rates (up to 15 s[-1]). Such a system will be valuable in the elucidation of the mechanisms of mechanical trauma and determination of injury tolerance criteria on a cellular level utilizing appropriate mechanical injury parameters.

Brain Injuries↗
PubMedDate not supplied

The duality of the inflammatory response to traumatic brain injury.

One and a half to two million people sustain a traumatic brain injury (TBI) in the US each year, of which approx 70,000-90,000 will suffer from long-term disability with dramatic impacts on their own and their families' lives and enormous socio-economic costs. Brain damage following traumatic injury is a result of direct (immediate mechanical disruption of brain tissue, or primary injury) and indirect (secondary or delayed) mechanisms. These secondary mechanisms involve the initiation of an acute inflammatory response, including breakdown of the blood-brain barrier (BBB), edema formation and swelling, infiltration of peripheral blood cells and activation of resident immunocompetent cells, as well as the intrathecal release of numerous immune mediators such as interleukins and chemotactic factors. An overview over the inflammatory response to trauma as observed in clinical and in experimental TBI is presented in this review. The possibly harmful/beneficial sequelae of post-traumatic inflammation in the central nervous system (CNS) are discussed using three model mediators of inflammation in the brain, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta). While the former two may act as important mediators for the initiation and the support of post-traumatic inflammation, thus causing additional cell death and neurologic dysfunction, they may also pave the way for reparative processes. TGF-beta, on the other hand, is a potent anti-inflammatory agent, which may also have some deleterious long-term effects in the injured brain. The implications of this duality of the post-traumatic inflammatory response for the treatment of brain-injured patients using anti-inflammatory strategies are discussed.

Animals↗
PubMedDate not supplied

Age does not influence DNA fragmentation in the hippocampus after fatal traumatic brain injury in young and aged humans compared with controls.

Paraffin sections from the hippocampus of 12 head-injured patients (Group A, aged between 4 and 12 years n = 6 and Group B, aged between 64 and 89 years n = 6) and associated age-matched controls were stained by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) technique for evidence of in-situ DNA fragmentation. TUNEL+ cells were of 2 Types: I (non-apoptotic) and II (apoptotic). In addition sections stained H&E, combined Luxol Fast Blue/Cresyl Violet and by immunohistochemistry for astrocytes (GFAP) and macrophages (CD68) were used to characterize the lesions. Small numbers of Type I TUNEL+ cells were seen in all sectors of the hippocampus except CA2 of both Groups A and B. Type II TUNEL+ cells were mainly found in the white matter. They constituted less than 1% of all TUNEL+ cells. There were similar or fewer TUNEL+ cells in the corresponding areas in the controls compared with the head-injured patients. However, in the dentate fascia and the CA4 sector of the Group B cases, larger numbers of TUNEL+ cells were seen in controls than after trauma. In the grey matter most TUNEL+ cells had the morphology ofnecrosis that corresponded with foci of selective neuronal damage. Only a few TUNEL+ cells were seen in white matter. The occasional Type I TUNEL+ cells were seen in grey matter. It is concluded that the amount and distribution of DNA fragmentation in children and adults is similar and therefore at least in the hippocampus does not provide an explanation for age as an independent variable of outcome after traumatic brain injury in childhood.

Age Factors↗
PubMedDate not supplied

No evidence for the presence of apolipoprotein epsilon4, interleukin-lalpha allele 2 and interleukin-1beta allele 2 cause an increase in programmed cell death following traumatic brain injury in humans.

BACKGROUND: Brain injury after trauma is an important cause of mortality and morbidity in society. There is evidence in both man and laboratory animals that in addition to necrosis, cell loss may occur as a result of programmed cell death (PCD). The cellular and molecular responses after head injury are partly influenced by genetic polymorphisms of apolipoprotein E and the pro-inflammatory cytokine IL-I. AIM: The principal aim of this study was to determine whether the presence of the ApoE epsilon4, IL- 1 alpha2 or IL- 1beta2 allele types influenced the amounts of PCD after head injury compared with controls. METHODS: Paraffin sections from the hippocampus of 38 patients (32 M : 6 F, aged 15 - 75, mean 38 years, survival 7- 576 hours; mean 36 hours) who died after a head injury were stained by Tunel histochemistry and quantified, and genotyping was undertaken by PCR "blind" to clinical detail. RESULTS: There were more Tunel+ cells (neurons and glia) after head injury than in controls with statistically increased numbers in all sectors of the hippocampus including the dentate fascia. However, there was no correlation between ApoEepsilon4, IL- 1 alpha allele 2 and IL- 1beta allele 2 and the amount of Tunel positivity. CONCLUSION: Given that both the ApoE and IL-1 influence outcome after various forms of acute brain injury, further work will be required to determine the mechanism underlying this relationship.

Adolescent↗
PubMedDate not supplied

The effects of surgery on the circadian rhythms of cortisol.

The circadian rhythms of plasma cortisol levels are studied extensively. Frequent sampling techniques are used to examine the effects of surgical trauma on the circadian pattern of plasma cortisol in man. Five patients were studied, 48 hours before and 48 hours after major surgery. The normal preoperative cortisol rhythms of these patients did not disappear after surgical trauma but they were significantly phase-shifted. In addition, the mean cortisol concentrations were significantly elevated and the intracircadian cycles suffered complex changes in the postoperative period.

Adult↗