Rage, rage against the dying of the light: a lament for needless death.
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Adult↗
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[Amphetamine--induced rage reaction in mice and its mechanism].
Rage reaction was induced in mice by ip amphetamine sulfate (APT) 15 mg/kg. Mice appeared hyperreactive after 6 min and then squeaked and fought each other. These manifestations were most distinct in 15-30 min and subsided after 40-70 min. At 20 degrees C and 25 degrees C, the occurrence of rage reaction was 85.0% and 90.0% respectively. The ED50 of APT for eliciting rage reaction was 11.8 +/- 2.1 mg/kg ip. No significant difference in the induction of rage reaction was observed between male and female mice but ambient temperature affected the occurrence of this reaction. Neuroleptic drugs (chlorpromazine, haloperidol, tardan and clozapine), anxiolytic drugs (diazepam and meprobamate) and reserpine suppressed the rage reaction induced by APT in mice. Phenobarbital and pentobarbital (at sedative doses), atropine, scopolamine, phentolamine and propranolol exerted no influence on APT--induced rage reaction. Amantadine, levodopa and apomorphine at lower doses potentiated the rage inducing effect of APT. Moreover, at higher doses amantadine or levodopa alone also evoked rage reaction similar to that induced by APT. Therefore, it may be deduced that the APT-induced rage reaction results from increased release of dopamine in limbic system and has nothing to do with the simultaneous epinephrine release. The available data indicate that the APT--induced rage reaction in mice deserves to be recommended as an animal model for screening potential neuroleptic drugs. The merits and shortcomings of this new model are discussed.
Amphetamine↗
Role of NMDA receptors in hypothalamic facilitation of feline defensive rage elicited from the midbrain periaqueductal gray.
The present study tested the hypothesis that the pathway from the medial hypothalamus to the midbrain periaqueductal gray (PAG) subserving defensive rage behavior in the cat facilitates the occurrence of this response when elicited from the PAG by utilizing excitatory amino acids as a neurotransmitter or neuromodulator. Cannula electrodes were implanted into the PAG for the elicitation of defensive rage behavior as well as for microinjections of excitatory amino acid antagonists and N-methyl-D-aspartic acid (NMDA). Monopolar stimulating electrodes were also implanted into the medial hypothalamus from which this response could also be elicited and, when stimulated at subthreshold levels for elicitation of behavior, could also facilitate the occurrence of PAG elicited defensive rage. Initially, dual stimulation of the PAG and medial hypothalamus facilitated the occurrence of defensive rage elicited from the PAG. Then, the identical dual stimulation paradigm was repeated with the same current parameters following the infusion of various antagonists for different receptors into the PAG defensive rage sites. The results indicate that infusion of either kynurenic acid [(0.1-2.0 nmol), a non-selective excitatory amino acid receptor antagonist] or D-2-amino-7-phosphonoheptanoic acid (AP7) [(0.1-2.0 nmol), a specific NMDA receptor antagonist], produced a dose and time dependent blockade of the facilitatory effects of medial hypothalamic stimulation. In contrast, microinjections of relatively larger doses of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) [(4 nmol), a non-NMDA receptor (quisqualate and kainate) antagonist] or atropine [(4.4 nmol), a muscarinic receptor antagonist] had little effect upon medial hypothalamically elicited facilitation of the PAG response. In a second experiment, NMDA [0.1-1.0 nmol] was microinjected directly into PAG defensive rage sites in the absence of medial hypothalamic stimulation. In these animals, drug infusion mimicked the effects of dual stimulation by producing a dose and time dependent decrease in response latencies. A third experiment was designed to further test the hypothesis by neuroanatomical methods. Here, the retrograde label, Fluoro-Gold, was microinjected into defensive rage sites within the PAG and following a survival time of 5-6 days, the animals were sacrificed. The brains were then processed for immunocytochemical analysis of cells that immunoreact positively for aspartate and glutamate. The results indicated the presence of many retrogradely labelled and immunocytochemically positive cells within the rostro-caudal extent of the medial hypothalamus as well as others that were double labelled.(ABSTRACT TRUNCATED AT 400 WORDS)
2-Amino-5-phosphonovalerate↗
[4-aminopyridine induced rage reaction in mice].
Rage reaction was induced in mice by sc 4-aminopyridine (4-AP) 6 mg . kg-1. Mice appeared hyperreactive after 8-12 min and then squeaked and fought each other. These manifestations were most distinct in 10-30 min and subsided after 40-60 min. The occurrence of rage reaction on this dose level was around 90%. At higher doses 4-AP caused convulsions and death after evocation of rage reaction. The ED50 of 4-AP for eliciting rage reaction was 4.7 +/- 0.7 mg . kg-1 sc. No significant difference in induction of rage reaction was seen between male and female mice of different body weights. Both neuroleptic drugs (chlorpromazine, haloperidol, tarden and clozapine) and anxiolytic drugs (diazepam, chlordiazepoxide, and meprobamate) inhibited 4-AP-induced rage reaction in mice. Barbiturates, Chloral hydrate, methaqualone, morphine hydrochloride, aspirin, phenytoin sodium, diphenhydramine hydrochloride, atropine sulfate, and procaine hydrochloride did not affect rage reaction. The 4-AP-induced aggressive behavior, similar to that induced by electric footshock or isolation, has the merits of convenience to deal with and time saving. Hence we recommended it as a screening method for drugs with neuroleptic and anxiolytic activities.
4-Aminopyridine↗
Advanced glycation end products drive blood-brain barrier lipid dysregulation via RAGE-ABCA1 signaling to promote neurovascular dysfunction in Alzheimer's disease.
Neurovascular dysfunction is an early and critical contributor to Alzheimer's disease (AD), yet the molecular mechanisms linking vascular pathology to metabolic dysregulation remain incompletely understood. Advanced glycation end products (AGEs), which accumulate during aging and metabolic stress, have been implicated in AD pathology; however, their role in cerebrovascular lipid homeostasis is unclear. Here, we demonstrate that AGE accumulation within cerebral microvessels promotes lipid droplet (LD) formation in endothelial cells through receptor for AGE (RAGE)-dependent disruption of cholesterol efflux pathways. In aged APP transgenic mice and human AD brains, we observe increased AGE deposition concomitant with elevated RAGE, DGAT1, and perilipin expression, alongside reduced ABCA1 levels. In human brain endothelial cells, AGE exposure induces lipid metabolic reprogramming characterized by enhanced LD accumulation, upregulation of lipogenic machinery, and suppression of cholesterol efflux. Mechanistically, RAGE silencing restores ABCA1 expression and attenuates LD formation, identifying RAGE as a key upstream regulator. Pharmacological activation of ABCA1 reverses AGE-induced lipid accumulation and reduces RAGE expression, highlighting a therapeutic axis. Furthermore, AGE exposure disrupts blood-brain barrier (BBB) integrity and impairs amyloid-β transport in an in vitro BBB model. In vivo, aging is associated with progressive microvascular LD accumulation, linking metabolic dysfunction to vascular pathology. Together, our findings establish an AGE-RAGE-ABCA1 signaling axis that drives endothelial lipid dysregulation and BBB impairment, providing a mechanistic framework connecting metabolic stress to neurovascular dysfunction in AD.
Journal Article↗
Magnetization prepared rapid gradient-echo (MP-RAGE) MR imaging of the liver: comparison with spin-echo imaging.
We have implemented an MR technique that employs a rapid gradient echo sequence, preceded by magnetization preparation pulses to provide T1- and T2-weighted tissue contrast. With this technique, which can be identified as a member of a new family of pulse sequences, generically named Magnetization Prepared RApid Gradient Echo (MP-RAGE), very short repetition times are used, allowing acquisition times of less than one second and images virtually free of motion-induced artifacts during quiet respiration. Fifteen patients with known liver lesions (metastases, hemangiomas, and cysts) were examined using T1- and T2-weighted 2-dimensional MP-RAGE sequences, and the images were compared with conventional T1- and multi-echo T2-weighted spin-echo (SE) sequences. Signal difference-to-noise ratios (SD/Ns) of the lesions were calculated for all pulse sequences using corresponding axial images and were normalized for voxel volume. The mean normalized SD/Ns of the MP-RAGE sequences were generally comparable to those for the SE sequences. In addition, there were no noticeable respiratory artifacts on the MP-RAGE images whereas these were clearly present on the T2-weighted SE images and to a lesser degree on the T1-weighted SE images. It is concluded that the MP-RAGE technique could become an important method for evaluating the liver for focal disease.
Cysts↗
The effect of thermic stress on the somatic reaction of rage and on rapid circling turns, in the cat.
An investigation was made of the effect of thermic stress on the somatic rage reaction and on rapid circling turns in cats awake and free to move in a behavioural cage. An increase in room temperature had a two-phase effect on the excitability of the nervous structures stimulated that is able to evoke the somatic rage reaction and rapid circling turns. The first phase, at room temperature 25 degrees-30 degrees C, was characterized by hypoexcitability; the second phase, appearing after longer periods of exposure and at temperatures above 30 degrees C, was characterized by the onset panting, hyperexcitability of the nervous structures stimulated and then by lowering of the somatic rage reaction threshold and a very significant increase in the number of circling turns. Experimentation on the action of cold external temperature on the excitability of structures involved in evoking the somatic rage reaction and rapid circling turns indicated an increase in their excitability, corresponding to an increase in spontaneous and evoked somatic motor activity.
Anger↗
Clinical comparison of three-dimensional MP-RAGE and FLASH techniques for MR imaging of the head.
Three-dimensional (3D) MP-RAGE (magnetization-prepared rapid gradient-echo) imaging was evaluated as a high-resolution 3D T1-weighted brain imaging technique for patients with suspected neurologic disease. Fourteen patients were studied. In five, 3D MP-RAGE images were compared with 3D FLASH (fast low-angle shot) images. Signal difference--to-noise ratios and T1 contrast were not statistically different for 3D MP-RAGE images as opposed to 3D FLASH images. Advantages intrinsic to the application of 3D MP-RAGE sequences include decreased imaging time and decreased motion artifact. With this technique, it is possible to perform a relatively motion-insensitive, T1-weighted screening brain study with voxel resolution of 1.0 x 1.4 x 2.0 mm or smaller, in an imaging time of 5.9 minutes or less--permitting offline (poststudy) reconstruction of high-resolution images in any desired plane.
Brain↗
MP RAGE: a three-dimensional, T1-weighted, gradient-echo sequence--initial experience in the brain.
The authors evaluated a recently developed sequence for magnetic resonance imaging of the brain. The three-dimensional, Fourier-transformed acquisitions require magnetization-prepared 180 degrees radio-frequency pulses and rapid gradient-echo (MP RAGE) sampling. The resulting T1-weighted images were compared with T1-weighted spin-echo (SE) images; both were obtained after paramagnetic contrast material was administered to 33 patients with known or suspected focal brain lesions. Image quality and contrast between gray and white matter were superior with the MP RAGE sequence compared with the T1-weighted SE sequence. The time for obtaining contiguous thin-section (1.3-2.5-mm) images was also comparable, with readily acquired multiplanar reformations obviating additional images. MP RAGE imaging depicted more focal lesions than did T1-weighted SE imaging and matched the number seen with T2-weighted SE imaging. Demonstration of paramagnetic contrast enhancement of lesions was comparable in most cases; however, three lesions showed greater enhancement on T1-weighted SE images and two others were seen only on the T1-weighted SE images. Thus, the MP RAGE sequence may provide an alternative to T1-weighted SE imaging.
Adult↗
Grief and rage: collective emotions in the politics of peace and the politics of gender in Israel.
Collective emotions of rage and grief dominate Israeli political discourses regarding the Middle East conflict. The weekly peace vigils of the Women in Black who protest the state's occupation of the West Bank and Gaza and the opposition which the vigils encounter, publicly display politicized collective emotions. In these weekly confrontations, grief and rage articulate intense contestations regarding the politics of peace as well as the politics of gender in Israel. Rage and grief unravel two drastically different visions of transcending national vulnerabilities and two disparate constructions of gender identity.
Emotions↗
Evaluation and treatment of rage in children and adolescents.
Rage is characterized by an unpredictable and primitive display of violence that is out of proportion to the provoking event and often threatens serious self-injury or harm to others. New insight into the pathogenesis of unpredictable violent behavior has been gained largely as a result of neurochemical, neuropsychological and brain imaging studies. This article examines episodic rage from a neuropsychiatric perspective. Three cases illustrating the evaluation and treatment of rage in childhood and adolescence are presented.
Adolescent↗
Rapid three-dimensional T1-weighted MR imaging with the MP-RAGE sequence.
The authors investigated the application of three-dimensional (3D) magnetization-prepared rapid gradient-echo (MP-RAGE) imaging to the acquisition of small (32 x 128 x 256) T1-weighted 3D data sets with imaging times of approximately 1 minute. A theoretical model was used to study the contrast behavior of brain tissue. On the basis of these theoretical results, 3D MP-RAGE sequences were implemented on a 1.5-T whole-body imager. Thirty-two-section 3D data sets demonstrating good signal-to-noise ratios and resolution and strong T1-weighted contrast were obtained in 1 minute. Compared with standard short TR/TE spin-echo sequences with the same imaging times and comparable sequence parameters, the 3D MP-RAGE sequence delivered increases of more than 50% in the white matter/gray matter signal difference-to-noise and white matter signal-to-noise ratios, and provided almost twice as many sections. These sequences may find a clinical role in 3D scout imaging and screening and in patients with claustrophobia or trauma.
Brain↗
Borderline rage and the therapist's reponse.
Borderline patients often engender feelings ranging from apathy to rage in therapists. The author views the borderline patient's rage as defensive against fear of total negation resulting from projective identification with hostile part objects. The therapist's withdrawal or anger parallels the patient's projection of affect. Countertransference offers the potential for understanding a patient's terror, but therapists may become fixed in identifications that distort their understanding. Clarity often comes slowly as the therapist directs attention to his/her own affective state in order to understand the patient's vulnerability.
Affect↗
Psychological factors in the etiology of ulcerative colitis: objectlessness and rage.
In this second investigation of psychological factors in the etiology of ulcerative colitis, the author again utilizes unusual cases characterized by limited variables preceding illness. The first investigation involved several patients whose partial deafness antedated their illness. A significant point was that prior to developing their illness, all these patients had arrived at a state of objectlessness which was abetted by the deafness. This report presents four ulcerative colitis patients with pre-existing organic problems affecting their mental status. Two of the patients are severely mentally retarded. A third patient has rapidly advancing multiple sclerosis, and a fourth--actually an addition to the earlier study--has long-standing partial deafness. Aside from the objectlessness which was also prominent in the earlier group, all four patients demonstrate a consistent pattern of vicious self-directed rage. This paper takes into account the interaction between the rage and the state of objectlessness in the production of illness.
Adult↗
The pharmacologic treatment of conduct disorders and rage outbursts.
Although this article focuses on psychopharmacology, pharmacotherapy is only part of a comprehensive treatment program. Treatment should be individualized to the patient's condition and level of intellectual functioning (e.g., conduct disorder, mental retardation). Clinicians should be acquainted with the Food and Drug Administration's regulations and the Physician's Desk Reference's guidelines. Psychoactive agents should be prescribed judiciously under careful clinical and laboratory monitoring, especially when given on a long-term basis. Knowledge of potential short- and long-term side effects is imperative to minimize impairment (cognitive, sedation) and to maximize achievement of adaptive behaviors. Aggressiveness is a low-frequency behavior and therefore difficult to assess. Aggressiveness with an explosive affective component and rage seems to be more responsive to pharmacotherapy than aggressiveness alone. Children who present with covert conduct disorder symptoms, such as stealing and lying, might not be as responsive to psychoactive agents as the conduct disorder with explosive characteristics. The neuroleptics are considered the standard drugs for the treatment of aggression but sedation and concern over tardive dyskinesia have led investigators to explore and study other classes of drugs. Lithium carbonate has been studied in short-term clinical trials and has been shown to be an effective alternative to the neuroleptics. Carbamazepine and propranolol seem to be promising agents but require further critical assessment in children and adolescents. Stimulants should be considered the first choice of treatment in coexisting conduct disorder and ADHD or in milder forms of aggression. In conclusion, there is a need for systematic investigation of the effectiveness and safety of psychoactive agents in children and adolescents with aggressiveness, explosiveness, and rage outbursts. There is some supportive evidence that some patients with these target symptoms are good responders to certain drugs. Future research should compare pharmacotherapy to psychosocial treatment and the combination of both.
Animals↗
Addiction, helplessness, and narcissistic rage.
In many cases addictive behavior serves to ward off a sense of helplessness or powerlessness via controlling and regulating one's affective state. Addicts have a vulnerability to feelings of powerlessness, which reflects a specific narcissistic impairment. The drive in addiction to re-establish a sense of power is, correspondingly, impelled by narcissistic rage. This rage gives to addiction some of its distinctive clinical properties. The narcissistic vulnerability in addicts is discussed. Several brief clinical cases are provided, and the view proposed is correlated with other psychoanalytic perspectives.
Adult↗
Sphenopalatine (nasal) ganglion: remote effects including "psychosomatic" symptoms, rage reaction, pain, and spasm.
Many articles implicate the nasal ganglion in the production of remote symptoms and discuss treatment. Symptoms are primarily spastic, involving both visceral and voluntary muscles including muscle spasm in the neck, shoulder, and low back; asthma, hypertension, intestinal spasm; diarrhea, angina pectoris, uterine spasm; intractable hiccup, and many others. All these symptoms appear to have 2 common denominators. They are mediated by the autonomic nervous system and at least in some instances can be "psychosomatic." The sphenopalatine ganglion (SPG) is a major autonomic ganglion located superficially in the pterygopalatine fossa, with major afferent distribution to the entire nasopharynx and important connections with the trigeminal nerve, facial nerve, internal carotid artery plexus of the sympathetic nervous system and, as shown in the rat, direct connection with the anterior pituitary gland. This paper presents arguments supporting the following hypotheses: 1. The SPG probably has a crucial role in lower animals in declenching the reflex responses known collectively as the rage reaction. 2. The SPG is a major point of entry to the autonomic system exposed to pathologic influences and readily accessible for therapeutic influences and readily accessible for therapeutic intervention. 3. A wide variety of symptoms are produced or maintained by alteration in autonomic system tonus and some of these may be affected by intervention on the SPG. 4. The possible relationship of some symptoms and "psychosomatic" conditions to the autonomic nervous system and the rage reaction must be considered.20
Anger↗
Selective versus nonselective preparation pulses in two-dimensional MP-RAGE imaging of the liver.
The use of a section-selective preparation pulse in two-dimensional (2D) T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE) imaging of the liver was investigated. The images were compared with those obtained with a nonselective pulse. The performances of the sequences were evaluated in 11 patients with 12 focal liver lesions, and lesion-liver and lesion-vessel signal difference-to-noise ratios (SD/Ns) were calculated. With the section-selective preparation pulse, small lesions were better differentiated from vessels, and multiple, consecutive images could be obtained at shorter intervals. The mean lesion-liver SD/N was slightly but not significantly greater for images obtained with a selective pulse, while the lesion-vessel SD/N was significantly greater (P less than .01). It is concluded that a section-selective preparation pulse can improve the clinical utility of the 2D MP-RAGE sequence in the evaluation of focal liver disease.
Humans↗