Increased vulnerability of the mildly traumatized rat brain to cerebral ischemia: the use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury.

Fasted Wistar rats were subjected to either a mild mechanical injury, 6 min of transient forebrain ischemia, or a mild mechanical injury followed 1 h later by 6 min of forebrain ischemia. EEG and evoked potentials were assessed intermittently and morphological analyses were performed after 7 days postinjury survival. In all groups complete qualitative recovery of electrical activity and general behavior was observed with 7-day survival. However, rats subjected to combined concussion and ischemia displayed EEG spike activity and a delayed return of EEG and evoked potentials during acute recovery not evident in other groups. No overt neuronal cell loss was seen in trauma alone and was minimal or absent in ischemia alone. However, extensive bilateral CA1 and subicular pyramidal cell loss was found in the septal and mid-dorsal hippocampi in the combined trauma and ischemia group. In contrast, no overt axonal injury was found in any group. We conclude that even mild mechanical injury can potentiate selective ischemic hippocampal neuronal necrosis in the absence of overt axonal injury. This potentiation also occurs in conjunction with more generalized electrophysiological disturbances such as EEG evidence of postischemic neuronal hyperactivity suggesting that mild concussion may also decrease the threshold for post-ischemic neuronal excitation. These results suggest the potential of this model for examining common or different injury mechanisms in mechanical and ischemic brain injury.

Combined pretrauma scopolamine and phencyclidine attenuate posttraumatic increased sensitivity to delayed secondary ischemia.

Fasted Wistar rats were given a mild level of traumatic brain injury (TBI) and then subjected to 6 min of transient forebrain ischemia 24 h posttrauma. One group was given simultaneous 1 mg/kg scopolamine and 4 mg/kg phencyclidine intraperitoneally (IP) 15 min before trauma and another group an equal volume of plasmalyte A solution. After 7 days of postinjury survival, placebo-treated rats demonstrated increased posttraumatic vulnerability to secondary ischemic CA1 neuronal death even 24 h after trauma. This finding confirmed that increased posttraumatic ischemic vulnerability persists for at least 24 h even following mild trauma. Combined muscarinic receptor and N-methyl-D-aspartate (NMDA) receptor coupled ion channel blockade given and present during the mild TBI statistically attenuated this enhanced secondary ischemic CA1 neuronal death and thus posttraumatic increased ischemic vulnerability. Placebo-treated rats had 335.3 +/- 93.6 CA1 neurons/10(6) microns 2 and drug-treated rats had 844.8 +/- 184.9 CA1 neurons/10(6) microns 2. This result suggests that muscarinic and/or NMDA receptor-mediated events confined to TBI and the early posttraumatic period are in part responsible for the phenomenon of increased posttraumatic ischemic vulnerability.

Effects of experimental fluid-percussion injury of the brain on cerebrovascular reactivity of hypoxia and to hypercapnia.

To test the hypothesis that concussive brain injury interferes with the normal vasodilator response of the cerebral circulation to hypoxemia, 30 cats were subjected to mild (PaO2 50 mm Hg) and severe (PaO2 30 mm Hg) hypoxemia while measurements were made of arterial and intracranial pressure, regional cerebral blood flow (CBF), and arterial blood gases. Ten cats served as controls, 10 were subjected to mild fluid-percussion injury of the brain (0.8 to 1.7 atmospheres (atm)), and 10 to severe injury (2.4 to 4.1 atm). The CBF response to hypercapnia (PaCO2 50 mm Hg) was also tested in most animals, and the response of CBF autoregulation to hemorrhagic hypotension was tested in four animals of each group. Trauma was found to severely attenuate the capacity of CBF to increase during hypoxemia. Responsiveness to hypoxemia appeared to be better preserved in traumatized animals than was autoregulation, but was less robust than the response to hypercapnia.

The role of postischemic recirculation in the development of ischemic neuronal injury following complete cerebral ischemia.

The neuronal response to complete cerebral ischemia (CCI) of 5-15 min duration was evaluated at the light and electron microscopic level subsequent to postischemic recirculation periods of up to 60 min. Following postischemic reperfusion, the homogeneous neuronal changes characteristic of permanent CCI were modified into a heterogeneous pattern of selectively vulnerable neuronal responses. Four basic types of neuronal injury were represented within this heterogeneous neuronal population. The Type I neuronal response was most numerous and consisted of chromatin clumping, nucleolar condensation and a breakdown of polysomes. This response may represent a reversal of some of the neuronal changes observed after permanent CCI. In addition to the above changes, Type II neurons contained swollen mitochondria and Golgi saccules which appeared as microvacuoles under the light microscope. Type III neurons displayed varying degrees of neuronal shrinkage and numerous swollen mitochondria. Type IV neurons were markedly shrunken and electron-dense with few identifiable subcellular structures. The distribution of Type I neurons was random but the other neuronal responses occurred in "selectively vulnerable" brain regions. The number of Type II, III, and IV neurons increased with extended insult durations but were unaffected by the length of recirculation. Ten minutes of CCI represented the threshold for a significant increase in the number of severely altered neurons. These findings suggest that considerable neuronal injury may be present after 10-15 min of CCI, and the lack of a recirculation period following CCI appears to afford the brain parenchyma an extensive degree of structural protection.

Autoregulation of cerebral blood flow after experimental fluid percussion injury of the brain.

To test the hypothesis that concussive brain injury autoregulation of cerebral blood flow (CBF), 24 cats were subjected to hemorrhagic hypotension in 10-mm Hg increments while measurements were made of arterial and intracranial pressure, CBF, and arterial blood gases. Eight cats served as controls, while eight were subjected to mild fluid percussion injury of the brain (1.5 to 2.2 atmospheres) and eight to severe injury (2.8 to 4.8 atmospheres). Injury produced only transient changes in arterial and intracranial pressure, and no change in resting CBF. Impairment of autoregulation was found in injured animals, more pronounced in the severe-injury group. This could not be explained on the basis of intracranial hypertension, hypoxemia, hypercarbia, or brain damage localized to the area of the blood flow electrodes. It is, therefore, concluded that concussive brain injury produces a generalized loss of autoregulation for at least several hours following injury.

[Changes in cerebrospinal fluid pressure in patients with hydrocephalus of various intensities]. / Zmiany cisnienia plynu mózgowo-rdzeniowego (CPMR) chorych z wodoglowiem o róznym stopniu nasilenia.

In 12 patients with hydrocephalus caused by posterior fossa tumours continuous measurements of intraventricular CSFP were done before and after implantation of ventriculoatrial valve and after tumour removal. A fall of the mean CSFP from 31.57 mm Hg to 15.32 mm Hg was observed after valve implantation, and a further fall of the mean CSFP to 10.55 mm Hg after removal of the tumour. After valve implantation pathological A and B waves disappeared. Absence of improvement after different stages of treatment indicated poor functioning of the valve, but it was observed also in patients with inoperable tumours.

[Cerebrospinal fluid pressure measurements in the ventricular system during and after surgery in patients with supratentorial brain tumors]. / Ocena wartosci pomiaru cisnienia plynu mózgowo--rdzeniowego (cpmr) w ukladzie komorowym podczas zabiegu operacyjnego i w okresie pooperacyjnym u chorych z nadnamiotowymi guzami mózgu.

In the light of CSFP measurements by Lundberg's method in 46 patients the authors showed the role of hyperventilation in lowering of intracranial pressure. A considerable efficacy of dexamethasone was demonstrated as well, the use of this drug permitted to achieve stabilization of CSFP during and after the operation. The investigations showed a considerable effectiveness of such drugs as mannitol and furosemide in lowering of CSFP. Pancuronium was found to be superior to suxamethonium for administration during induction of anaesthesia because the former caused no CSFP rise. In polygraphic investigations of nocturnal sleep with parallel recording of CSFP a rise of CSFP was demonstrated during REM phase of sleep.

Dynamics of the blood pressure changes in sodium nitroprusside induced controlled arterial hypotension in neurosurgery.

Dynamics of the arterial blood pressure changes under the influence of intravenous infusion of sodium nitroprusside (SN) were studied in 12 patients operated on for intracranial aneurysms. Adequate measures were undertaken to avoid blood pressure (BP) changes due to the anaesthetic procedure itself. It was found that the speed of BP lowering corresponded to the rate of infusion, and could easily reach 10 mm Hg/min. After stopping the infusion, the BP recovery rate averaged a mean speed of 8.5 mm Hg/min, varying from 3.8 to 12 mm Hg/min. High speeds of BP lowering and recovery achieved with the use of SN are the main advantages of this hypotensive agent in neurosurgical procedures.

Controlled arterial hypotension during neurosurgical operations.

Controlled arterial hypotension was applied in 62 hyperventilated patients during neurosurgical operations. Hypotension was obtained using trimetaphan (19 cases), trimetaphan and halothane (32 cases) and sodium nitroprusside (11 cases). It was found that the action of sodium nitroprusside was the quickest and lasted the shortest, which considerably facilitated the control of hypotension. Halothane permitted hypotension to be obtained rapidly but in certain cases it prolonged the hypotensive action of trimetaphan.

[Sodium nitroprusside in controlled arterial hypotension during neurosurgical operations]. / Zastosowanie nitroprusydku sodu do prowadzenia kontrolowanego podcisnienia tetniczego krwi w operacjach neurochirurgicznych

A 0.02% solution of sodium nitroprusside was given in intravenous drip infusion for induction of controlled arterial hypotension during intracranial operations. The drug was given to 9 patients operated upon for aneurysms and 2 patients with intracranial meningiomas. It was observed that arterial blood pressure could be easily controlled in this way for the purposes of operation.

Hyperventilation in neurosurgery.

An outline of the nature and varieties of hyperventilation is presented together with a discussion on the role of artificial hyperventilation in the management of neurosurgical patients. Attention is called to the value of gasometric investigations in the ventricular cerebrospinal fluid for evaluation of disturbances in pH of the intracranial environment and possible effectiveness of hyperventilation. The results of our measurements of cerebrospinal fluid pressure are presented in 21 cases of supratentorial cerebral tumours in which controlled ventilation with hyperventilation was conducted. In 19 cases, the cerebrospinal fluid pressure fell by a mean of 44.3% with a simultaneous fall of PaCO2 by 29.3%. In the conclusions the authors stress the role of hyperventilation in the lowering of raised cerebrospinal fluid pressure and prevention of cerebral oedema.