Concussive Head Research Articles

Coma associated with flaccidity produced by fluid-percussion concussion in the cat. I: Is it due to depression of activity within the brainstem reticular formation?

This study is the first attempt to characterize neurological and behavioural consequences of fluid-percussion concussive head injury in the cat. Both animals initially anaesthetized by N2O as well as unanaesthetized, chronically prepared animals were subjected to injury. Injury with a fluid-pressure wave of 1.9-2.5 atm (duration 21-24 ms) produced a brief generalized areflexia. Following this initial response, injury greater than 2.1 atm frequently produced a period associated with hypotonia of postural muscles and suppression of postural motor responses (flaccidity). A close association between flaccidity and other indices of coma such as absence of eye-opening responses was noted. These consequences of injury can occur without fatal apnoae, circulatory collapse or overt intraparenchymal haemorrhages. This result suggests that mechanical stress predominantly restricted to the brain stem in fluid percussion may be sufficient, at least in the cat, to produce coma associated with flaccidity which has been previously documented for acceleration concussion. There was no evidence that fluid percussion produced EEG depression similar to the effects of lesions in the mesencephalic reticular activating system (RAS). Thus, depression of general levels of brain activity including those within the RAS seems not be necessary for production of this form of reversible coma.

Regional rates of glucose utilization in the cat following concussive head injury.

Injections of [14C]-deoxyglucose ([14C]DG) were used to study rates of local cerebral glucose utilization (LCGU) in control cats and cats subjected to concussive brain injury produced by a fluid-percussion device. Studies in separate groups of animals demonstrated that the injury level selected produced transient behavioral suppression probably associated with traumatic disturbances of consciousness. LCGU was sampled near the site of fluid-percussion injury and more caudally in pontine regions. Histopathologic studies examined the possibility of hemorrhage, contusion, or breakdown of the blood-brain barrier in regions within which LCGU was calculated. These studies yielded analyses indicating that (1) the [14C]DG technique can be applied usefully to infer changes in regional levels of brain activity after concussion, (2) concussive injury produces changes in brain function that differ reliably across various regions of the central nervous system and may include both depression and focal activation of specific brain sites. Data are discussed that suggest that changes in brain activity in specific regions indicated by changes in LCGU could contribute to acute neurologic disturbances after concussion including unconsciousness.

Coma associated with flaccidity produced by fluid-percussion concussion in the cat. II: Contribution of activity in the pontine inhibitory system.

In the preceding paper we reported that concussive levels of fluid-percussion head injury can produce transient flaccidity of postural muscles associated with other indices of coma. This reversible coma associated with flaccidity follows an initial period of generalized areflexia and occurs in the absence of EEG slow waves. The present study investigated the physiological mechanisms underlying the flaccidity following concussive head injury be recording dorsal and ventral root potentials of the spinal cord. Studies indicated that, during the initial period of generalized areflexia, afferent input transmission was depressed although the excitability of motoneuronal pools was increased. In contrast, during periods of flaccidity, spinal cord somatomotor functions were depressed while transmission of afferent inputs was recovering. Systematic transection of the brain stem showed that activity within structures lying between collicular and midpontine levels is necessary to produce this latter condition. Cholinergic activation of pontine inhibitory areas within this same region of the rostral pons can produce profound descending inhibitory influences on postural somatomotor function in conjunction with other features of coma including suppression of eye-opening responses. Such effects occur without EEG slow waves. Moreover, other data indicate that local rates of glucose utilization within this pontine inhibitory area increase following concussive head injury. Thus, it is possible that a predominance of activity within the pontine inhibitory area could provide at least one neural basis for the reversible comatose state following concussive head injury characterized by close association between flaccidity and other indices of coma. Possible relationships of these data to clinically observed features of concussion are discussed.

Beneficial effects of the κ opioid receptor agonist U-50488H in experimental acute brain and spinal cord injury

The effects of the selective κ opioid receptor agonist U-50488H (trans-3,4-dichloro- N-methyl- N[2(pyrrolidinyl)-cyclohexyl]-benzeneacetamide) were examined in acute head and spinal injury models. First, in a blinded protocol, male CF-1 mice were treated intravenously with either saline or U-50488H (1, 3 or 10 mg/kg) within 3–5 min following a reproducible and quantifiable moderately severe (900 g/cm) concussive head injury. Using a grip test at 1 h postinjury to evaluate the neurological status of the injured mice, U-50488H produced a dose-related improvement in early recovery compared to the saline-treated mice. The effect was significant ( P < 0.05) after the 3 or 10 mg/kg i.v. doses. A similar concussive injury markedly reduced the % of cardiac output perfusing the forebrain (cerebral blood flow). U-50488H (10 and 20 mg/kg) partially reversed this effect to a significant degree 60 min after a 20 mg/kg dose. Secondly, the effects of U-50488H on the development of progressive post-traumatic spinal cord white matter ischemia after a 500 g/cm contusive injury were studied in pentobarbital-anesthetized cats. In 4 untreated cats, there was a progressive fall in spinal cord and blood flow (SCBF) from a 10-min postinjury level of 10.5 ± 0.7 ml/100 g/min to 6.1 ± 0.3 ( P < 0.03 by paired t at 4 h). In U-50488H-treated cats (3 mg/kg i.v. 30 min before plus 1 mg/kg i.v. at 1.5 h after injury), SCBF only declined from 10.4 ± 1.4 ml/100 g/min at 10 min postinjury to 9.1 ± 0.9 at 4 h ( P < 0.3). The mean SCBF was significantly higher ( P < 0.05 by Student's t-test) at 2 and 4 h postinjury in the U-50488H-treated cats compared to the untreated animals. The results imply that κ receptor activation may be beneficial in the injured nervous system rather than deleterious as other investigators have suggested.

Effects of a new TRH analogue, YM-14673 on the central nervous system

The effects of a new TRH analogue, YM-14673 (N alpha-[[S)-4-oxo-2-azetidinyl)carbonyl]-L-histidyl-L-prolinamide dihydrate) on the central nervous system were compared with those of TRH. YM-14673 was 10-40 times more potent than TRH in antagonizing pentobarbital-induced sleep and hypothermia, and ethanol-induced hypothermia in mice. YM-14673 accelerated recovery from disturbed consciousness induced by concussive head trauma in mice and normalized the behavior and spontaneous EEG disturbed by electrolytic lesion of the hypothalamus in cats with 25-100 times greater potency than that of TRH. In the tests on pentobarbital sleeping time and EEG disturbance, the cerebral activating activity of YM-14673 was 8-36 times longer-lasting than that of TRH. These results indicate that YM-14673 possesses potent arousal effects on the central nervous system. The mode of action of YM-14673 was also discussed.

A new model of concussive brain injury in the cat produced by extradural fluid volume loading: I. Biomechanical properties

This study presents a new device for producing experimental, concussive head injury together with a detailed description of biomechanical features of fluid percussion brain injury in the cat. Anaesthetized cats were subjected to multiple (N = 3) or single injuries (N = 87). The variables studied in repeated injury experiments included the volume of fluid injected intracranially, rate of fluid flow, and the associated pressure transients recorded extracranially in the injury device and intracranially at supratentorial and infratentorial sites. Peak fluid flow increased with increasing volumes of fluid loaded intracranially. Extracranial pressure peaks and durations increased when volume loading was increased. Extracranial and intracranial pressure transients were similar at all recording sites. The form of pressure transients recorded in single injury experiments was similar to that recorded in multiple injury experiments. In single injury experiments, the extracranial pressure peaks and durations also increased with increased intracranial fluid volume loading. The slopes describing the relationships between intracranial volume loading and extracranial pressure transients were significantly different in single and multiple injury experiments. Details of the design and use of the head injury device are also discussed.

Coma induced by Cholinergic Activation of a Restricted Region in the Pontine Reticular Formation

We previously demonstrated evidence suggesting increased neural activity in the pontine reticular formation ventromedial to the principal nucleus of locus coeruleus after experimental concussive head injury in the cat. We report here that microinjections of small doses of the cholinergic agonist carbachol (0.4 μg in 0.2 μl, bilaterally) into this restricted brain stem region of the awake cat produces a reversible, flaccid, comatose state analogous to that of the lowest score on the Glasgow Coma Scale, the grading system commonly employed in assessments of human coma. Microinjection of the local anesthetic tetracaine into the same region failed to produce detectable effects, and therefore the carbachol effects were probably due to activation of pathways within the injection sites that actively inhibit various aspects of the animals' responsiveness to the external environment. The flaccid, comatose state produced by carbachol was not the result of epileptic processes, since neither epileptic electroencephalographic discharges nor convulsive movements were observed. The muscarinic antagonist atropine reversed the carbachol effects. We shall also discuss possible implications of these data in terms of mechanisms of flaccid coma associated with good recovery in humans.

Concussive head injury producing suppression of sensory transmission within the lumbar spinal cord in cats.

This study examines the effects of concussive levels of a fluid-percussion head injury on sensory transmission within the lumbar spinal cord of the cat. Primary afferent depolarization (PAD) was suppressed for 2 to 5 minutes following injury, as assessed by dorsal root potentials and augmentation of antidromic dorsal root potentials, both evoked by stimulation of adjacent dorsal roots. Polysynaptic reflex discharges in ventral root potentials evoked by dorsal root stimulation were also profoundly suppressed during this same period, even when spontaneous and monosynaptic reflex discharges were facilitated. Changes in PAD produced by injury were abolished by spinal cord transection, but were not affected by midpontine transection. These findings suggest that concussive head injury can produce suppression of segmental sensory transmission by neurally mediated processes involving the bulbar brain stem. Recordings of dorsal root resting potentials, antidromic dorsal root potentials, and reductions of antidromic dorsal root potentials induced by tetanic root stimulation indicated that depressed segmental sensory function produced by injury was due to suppression of postsynaptic interneuronal transmission rather than to excitability changes in primary afferent fibers. Somatosensory cortical potentials evoked by dorsal root stimulation were profoundly depressed at the same time as segmental sensory transmission was suppressed, suggesting that suppressed segmental sensory transmission may also contribute to suppression of ascending sensory transmission. It is hypothesized that transmission failure of interneuronal systems in the initial period following insult may be a general response occurring in wide areas of the central nervous system, and not restricted to areas to which mechanical stress is directly applied. This response pattern may result from indiscriminate activation of interconnected excitatory and inhibitory elements of interneuronal systems.

Depression of afferent-induced primary afferent depolarization at the lumbar spinal cord following concussive head injury

Afferent-induced primary afferent depolarization (PAD) was depressed for 2–5 min following concussive head injury in the cat, as assessed by dorsal root potentials and augmentation of antidromic dorsal root potentials, both evoked by stimulation of adjacent dorsal roots. These changes in PAD were abolished by spinal cord transection but not affected by midpontine transection. Spontaneous dorsal root potentials, resting amplitudes of antidromic dorsal root potentials and reductions of antidromic dorsal root potentials following tetanic root stimulation were not substantially altered by injury. These findings suggest that concussive head injury depresses spinal interneuronal transmission by neurally mediated processes involving the bulbar brainstem.

Active Neural Processes within the Brain Stem in Production of Coma

During a series of studies of neural processes underlying coma following concussive head injury, we recognized processes similar to those originally termed coma-puncture by Araki et al. In this paper we will review the pioneer work by Araki and his colleagues in light of current information. The data from their studies and our own observations suggest that sudden, disorganized excitation of extensive areas in the pontomesencephalic region may be associated with neural sequences resulting in activation of neural systems that actively inhibit responsiveness to external stimuli and thereby produce coma.

γ-butyrolactone-γ-carbonyl-histidyl-prolinamide citrate (DN-1417) : A novel TRH analog with potent effects on the central nervous system

A novel TRH analog, γ-butyrolactone-γ-carbonyl-histidyl-prolinamide citrate (DN-1417) with very low TSH-releasing activity markedly increased motor activity in the mice, with and without reserpine administration. DN-1417 also promoted arousal from pentobarbital or ethanol sleep and from loss of consciousness induced by concussive head injury, and reversed hypothermia induced by pentobarbital and reserpine. Circling behavior was provoked by comparatively low doses of DN-1417 in mice with unilateral striatal lesion, and the effect was prevented by pimozide and α-methyl-p-tyrosine. The results indicate that DN-1417 is more potent and longer-acting than TRH in the CNS behavioral paradigms, and that some of the effects may be relevant to central monoaminergic systems.

Linkage studies in Van der Woude syndrome.

A newly ascertained kindred segregating Van der Woude syndrome through four generations is described. Linkage studies using the methods of Ott (1974) were carried out using 19 marker loci.

Near-Drowning From Ding-String Surfboarding: A Case Report

To the Editor.— Serious injuries including toe amputation, lacerations, and blunt trauma have been reported with the use of a surfboard leash or ding-string in surfboarding. 1 We would like to report the following case of a patient who had severe near-drowning while surfboarding with a ding-string. Report of a Case.— The patient was an 18-year-old experienced male surfer who suffered a concussive head injury and near-drowning in ocean water while surfboarding, surfboard leash attached, at Sandy Beach on Oahu. According to Oahu Emergency Medical Services protocol, he was rescued (in an unconscious state) from the ocean by first-responder trained lifeguards. He was resuscitated from ventricular fibrillation on the beach by trained Mobile Intensive Care Technician (MICT) ambulance paramedics using endotracheal intubation, electrical defibrillation, intracardiac epinephrine, intravenous sodium bicarbonate, thorough airway suctioning, and 100% oxygen delivered by positive pressure valve to the endotracheal tube. He was transported by the MICTs

Rate of cerebral energy consumption in concussive head injury in the rat.

The metabolic rate was determined in the rat brain during the immediate concussive response to standardized impact accelerations of 7 and 9 m/sec velocity. In one series, the metabolic state was determined in freeze-clamped cortical and brain-stem tissue 20 seconds after the impact. The metabolic rate was calculated from the rate of energy depletion in the adjacent unclamped tissue during 10 seconds of total ischemia. The freeze-clamping procedure per se was shown to enhance the metabolic rate probably by inducing mechanical excitation. In another series, in situ freezing was used for tissue sampling in the same situation. A 10-second period of heart standstill induced a standardized period of ischemia. During the acute concussive response to impact acceleration at 7 m/sec velocity, there was an increase of the metabolic rate in the brain stem. A more intense concussive impact at 9 m/sec velocity further enhanced this reaction and also involved the cortex. It is concluded that the basis of the immediate concussive response is a mechanically elicited neuronal excitation. This may lead to energy depletion unless the increased metabolic demands are met.

頭部外傷, 脳腫瘍の造血機能に及ぼす影響並びに造血機能の中枢性機制に関する臨床的, 実験的研究

The author investigated the hematopoietic activity in patients suffering from head injuries and brain tumors and made experimental studies on the existence and localization of the erythropoietic center in dogs.The erythropoietic activity was estimated in those patients by the number of reticulocytes in the peripheral blood and M: E ratio in the bone marrow. The erythropoietic activity was estimated in dogs by the number of reticulocytes, the number of erythroblasts and its mitotic activity in the bone marrow, after experimental head concussion, intrathecal air injection and stereotaxic electrocoagulation of various sites of the brain.1. Decrease of the erythropoietic activity was seen in 20per cent of 44 cases of head injury. There was no relation between the erythropoietic activity and clinical symptoms.2. Decrease of the erythropoietic activity was observed in 5 out of 57 cases of brain tumor. Three of 5 cases were those of tumor with diabetes insipidus, craniopharyngioma and third ventricle tumor. All cases of pituitary adenoma showed no remarkable decrease in the activity before or after operation. General operative stress, blood loss and transfusion had no definite relationship with the activity.3. Temporary decrease of erythropoiesis was observed in dogs with head concussion and intrathecal air injection.4. No change in erythropoiesis was noted in anesthetized or ACTH-Z injected dogs.5. A remarkable decrease of the erythropoietic activity followed the stereotaxic electrocoagulation of the diencephalon. Lesions of other areas showed no such changes.It is concluded that the erythropoietic center may exist in the diencephalon, although its exact localization needs further study.

MEASUREMENT OF EXPERIMENTALLY INDUCED BRAIN SWELLING AND SHRINKAGE

ArticleMEASUREMENT OF EXPERIMENTALLY INDUCED BRAIN SWELLING AND SHRINKAGEK. A. C. Elliott, and Herbert JasperK. A. C. ElliottFrom the Department of Neurology and Neurosurgery, McGill University, and the Montreal Neurological Institute, and Herbert JasperFrom the Department of Neurology and Neurosurgery, McGill University, and the Montreal Neurological InstitutePublished Online:01 Apr 1949https://doi.org/10.1152/ajplegacy.1949.157.1.122MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByTiO2-Nanowired Delivery of DL-3-n-butylphthalide (DL-NBP) Attenuates Blood-Brain Barrier Disruption, Brain Edema Formation, and Neuronal Damages Following Concussive Head Injury30 August 2017 | Molecular Neurobiology, Vol. 55, No. 1 More from this issue > Volume 157Issue 1April 1949Pages 122-129 Copyright & PermissionsCopyright © 1949 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1949.157.1.122PubMed18130228History Received 5 January 1949 Published online 1 April 1949 Published in print 1 April 1949 Metrics

THE ELECTROENCEPHALOGRAM IN EXPERIMENTAL CONCUSSION AND RELATED CONDITIONS

ArticlesTHE ELECTROENCEPHALOGRAM IN EXPERIMENTAL CONCUSSION AND RELATED CONDITIONSJames W. Ward, and Sam L. ClarkJames W. Ward, and Sam L. ClarkPublished Online:01 Mar 1948https://doi.org/10.1152/jn.1948.11.2.59MoreSectionsPDF (3 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByGenetic Background Influences Acute Response to TBI in Kindling-Susceptible, Kindling-Resistant, and Outbred Rats10 January 2020 | Frontiers in Neurology, Vol. 10Electrophysiologic recordings in traumatic brain injuryThe neurophysiology of concussionProgress in Neurobiology, Vol. 67, No. 4Regional Rates of Glucose Utilization in the Cat Following Concussive Head InjuryJournal of Neurotrauma, Vol. 5, No. 2Coma associated with flaccidity produced by fluid-percussion concussion in the cat. I: Is it due to depression of activity within the brainstem reticular formation?3 July 2009 | Brain Injury, Vol. 2, No. 1Metabolic and Neurophysiologic Sequelae of Brain Injury: A Cholinergic HypothesisCentral Nervous System Trauma, Vol. 3, No. 2Head injury in the champanzeeJournal of Neurosurgery, Vol. 39, No. 2ReferencesActa Psychiatrica Scandinavica, Vol. 30, No. S95Die Commotio cerebri als pathogenetisches und BegutachtungsproblemActa Neurovegetativa, Vol. 4, No. 4-5The electroencephalographic findings in 39 surgically proven subdural hematomaElectroencephalography and Clinical Neurophysiology, Vol. 3, No. 1 More from this issue > Volume 11Issue 2March 1948Pages 59-74 https://doi.org/10.1152/jn.1948.11.2.59PubMed18905648History Published online 1 March 1948 Published in print 1 March 1948 Metrics

PRESENCE AND ACTION OF ACETYLCHOLINE IN EXPERIMENTAL BRAIN TRAUMA

PRESENCE AND ACTION OF ACETYLCHOLINE IN EXPERIMENTAL BRAIN TRAUMA

Microscopic Neuronal Injury in Rats Submitted to Concussive Head Trauma Under Different Mechanisms.

SummaryRats recovering from a temporary period of unconsciousness, varying from 10 seconds to 15 minutes, following a blunt impact on the head which had left skull and brain apparently intact, frequently revealed microscopic evidence of neuronal injury affecting, in multiple areas, nerve cells, axis cylinders, and myelin sheaths, Using a trauma of the same strength, no differences were seen, either in the immediate effects or in the type and extent of cerebral changes, when the impact was delivered on the stationary head or on the head in rapidly accelerated motion.