C. K. Park

Spontaneous evolution of posttraumatic subdural hygroma into chronic subdural haematoma

SummaryThirteen of 145 patients with post-traumatic subdural hygroma (SDHy) developed chronic subdural haematoma (CSDH) at the involved site over a period of 6 years. CSDHs were found at the site of SDHys with no history of further head injury at a mean interval of 56 days. It appeared that these 13 patients did not have any distinguishing clinical features early on. Old age and brain atrophy on CT scans do not seem to be reasonable causative factors in the evolution of SDHy into CSDH. Initial enlargement of subdural accumulations at an early stage of SDHy and a subsequent increase in density at a later stage may point to the development of CSDH from SDHy in some instances. Ten of these 13 CSDH cases underwent surgical drainage, and the remaining 3 cases received no specific management. All resolved completely. The prognosis was good in all patients. The possible mechanism for the evolution of SDHy into CSDH is discussed.

Antiischemic effects of propentofylline (HWA 285) against focal cerebral infarction in rats

The effects of the xanthine derivative propentofylline (HWA 285), an inhibitor of adenosine transport, on ischemic brain damage have been evaluated in a model of permanent middle cerebral artery (MCA) occlusion in rats. During the postischemic survival period of 24 h, the animals were subjected to neurological and behavioral observations and then sacrificed to assess the extent of ischemic tissue damage by tetrazolium chloride. Posttreatment with propentofylline (0.01, 0.05 or 0.1 mg/kg/min, continuous i.v. infusion) initiated 15 min following MCA occlusion, produced significant reductions in infarct volumes; the highest being the most effective (reduction by 39%; P < 0.005) and improved the neurological symptoms when compared with an untreated control group. In contrast to other antiischemic agents, such as glutamate receptor antagonists, the drug induced no behavioral disturbances. This study indicates that propentofylline may provide neuroprotective effect against ischemic brain damage following stroke without negative behavioral side effects.

Efficacy of d-CPPene, a competitive N-methyl-d-aspartate antagonist in focal cerebral ischemia in the rat

The effect of a novel and potent competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (D-CPPene) upon ischemic brain damage has been examined in a rat model of focal cerebral ischemia. Focal cerebral ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). The animals were sacrificed 24 h after MCA occlusion and the amount of ischemic brain damage was assessed at 8 predetermined coronal planes. Pretreatment with D-CPPene (1.5, 4.5 or 15 mg/kg, i.v.), initiated 15 min prior to MCA occlusion (followed by constant infusion at 1, 3 or 10 mg/kg/h), produced dose-dependent reductions in the volumes of infarction; the dose of 4.5 mg/kg being the most effective (reduced by 37%; P < 0.01). These results indicate that systemic administration of the competitive NMDA antagonist D-CPPene has neuroprotective effects in a model of focal cerebral ischemia and define the dose dependency of its neuroprotective effects.

Pretreatment with a competitive NMDA antagonist D-CPPene attenuates focal cerebral infarction and brain swelling in awake rats

SummaryThe purpose of the study was to assess effects of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (D-CPPene) upon focal cerebral infarction and brain oedema in the rat. Focal cerebral ischaemia was produced by permanent occlusion of the middle cerebral artery under halothane anaesthesia. The anaesthetic gas was discontinued immediately after the occlusion and the rats were killed 24 hours later. Cerebral infarction and brain swelling were each assessed on the frozen brain sections at 8 predetermined coronal planes.Pretreatment with D-CPPene (4.5mg/kg i.v. followed by continuous infusion at 3mg/kg/h until sacrifice) 15 minutes prior to MCA occlusion, significantly reduced the volume of infarction in the cerebral hemisphere by 29% (p<0.05). Brain swelling, obtained by subtracting the nonischaemic hemispheric volume from the ischaemic hemispheric volume, was significantly reduced with D-CPPene treatment and the mean reduction in swelling (34% less than the controls: p<0.001) proportionately similar to the decrease in infarct volume in the same animals.These data indicate that systemic administration of the competitive NMDA receptor antagonist D-CPPene has neuroprotective effects against ischaemic brain damage, and the reduction in brain swelling occurs in parallel with the reduction in ischaemic damage.

Do N-methyl-D-aspartate Antagonists Have Disproportionately Greater Effects on Brain Swelling than on Ischemic Damage in Focal Cerebral Infarction?

Using a frozen section technique, we have assessed the effects of N-methyl-D-aspartate (NMDA) antagonist upon brain swelling caused by ischemic brain edema in a rat model of focal cerebral infarction. Although pretreatment with the competitive NMDA antagonist, D-CPPene or the noncompetitive NMDA antagonist, CNS 1102 reduced both the volumes of infarction and ischemic edema in the cerebral hemisphere, mean reduction in brain edema was proportionately similar to decrease in infarct volume in the same animals (correlation coefficient, r = 0.82, p < 0.001). There was, therefore, no evidence of disproportionately greater effects with NMDA antagonist upon brain edema.

Assessment of the relationship between ischemic damage and brain swelling in frozen brain slices.

The purpose of the study was to verify a method for the measurement of both cerebral infarction and brain swelling in frozen brain slices for histology. The animals were divided into two groups sham-operated control (n = 10) and focal cerebral ischemia group (n = 10). Focal cerebral ischemia was produced by permanent occlusion of the left middle cerebral artery. The rats were sacrificed 24 hours postocclusion. The brain was divided into two through the corpus callosum. Each hemisphere was weighted and frozen. Cerebral infarction and brain swelling were each assessed at 8 predetermined coronal planes. The volume of brain swelling was obtained by subtracting the total volume of nonischemic hemisphere from the total volume of the ischemic one. In the MCA occlusion group, brain infarction and the differences of hemispheric volume and weight between the right and left hemispheres were consistently observed, whereas sham-operated rats demonstrated no brain infarction or significant differences between two hemispheres. There were good corelationships not only between the volumes of brain edema and infarction (p < 0.05) but between the volume of brain edema and the difference in weight (p < 0.01) also. The results indicate that the measurement of the volume of ischemic brain edema in frozen brain slices may be useful in elusidating relationship with ischemic brain damage.

Diffuse Axonal Injury: Changes of Cerebral Blood Flow, Intracranial Pressure and Evoked Potentials

There are various types of diffuse brain damage as a consequence of nonmissile head injury, but it is likely that widespread tearing of nerve fibers occurs at the moment of injury in most of these patients. A number of synonyms have been proposed to denote this type of brain damage. Recently, “diffuse axonal injury (DAI)” was preferably used and the concept of DAI has been well recognized not only pathologically [1] but also clinically [2]. However, the details of its clinical features and its influence on prognosis remain to be elucidated. This prospective study was done to investigate the relationship of ICP, cerebral blood flow (CBF) and changes of multimodality evoked potentials (MEPs) with outcome in patients with DAI.

Effects of Respiratory Depression on Cytoprotective Effect of the Competitive NMDA Antagonist, D-CPPene

Numerous experimental data suggest that the excitatory amino acid neurotransmitter glutamate is involved in the pathophysiology of ischaemic neuronal injury [8] as well as traumatic brain injury [3], and that the glutamate subtype receptor, N-methyl-D-aspartate (NMDA) antagonists have cytoprotective effect against ischaemic neuronal damage [6]. Since secondary ischaemia is one of the major contributing factors in the pathology of traumatic injury of the brain and patients with head injury can arrive at a hospital at a time before the development of secondary ischaemia, it can be a promising therapeutic area for NMDA antagonists. However, many patients with severe head injury suffer from respiratory problems such as apnea, atelectasis and aspiration in acute stage, while in animal experiment an optimal physiological state has been emphasized. The objective of this study was to examine the effect of systemic acidosis induced by respiratory depression under halothane anesthesia upon the extent of ischaemic brain damage as well as upon the cytoprotective efficacy of the competitive NMDA receptor antagonist, (E)-4-(3-phosphonoprop-2-enyl)-piperazine-2-carboxylic acid(D-CPPene) in the middle cerebral artery occlusion (MCAO) model of rats.