The Effect of Simvastatin on the Dynamics of NF-κB-Regulated Neurodegenerative and Neuroprotective Processes in the Acute Phase of Ischemic Stroke.

Statins are lipid-lowering drugs that act by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase, a rate-limiting enzyme in cholesterol biosynthesis. Animal studies have shown neuroprotective effects of statins in cerebral stroke. However, the underlying mechanisms are not fully understood. The nuclear factor-kappa B (NF-κB) transcription factor is involved in the regulation of apoptosis in stroke. Different dimers of NF-κB regulate the gene expression of proteins involved in both neurodegeneration and neuroprotection. We aimed to determine whether simvastatin improves stroke outcome via inhibition of the RelA/p65-containing subunit and downregulation of stroke-induced pro-apoptotic genes or via activation of NF-κB dimers containing the c-Rel subunit and upregulation of anti-apoptotic genes during the acute stroke phase. Eighteen-month-old Wistar rats, subjected to permanent MCAO or sham surgery, were administered simvastatin (20 mg/kg b.w.) or saline for 5 days before the procedure. Stroke outcome was determined by measuring cerebral infarct and assessing motor functions. The expression of NF-κB subunits in various cell populations was investigated using immunofluorescence/confocal microscopy. RelA and c-Rel were detected by WB. The NF-κB-DNA binding activity was investigated using EMSA, and expression of Noxa, Puma, Bcl-2, and Bcl-x genes was analyzed by qRT-PCR. Results showed a 50% infarct size reduction and significant motor function improvement in the simvastatin-treated animals which correlated with a decrease in RelA and a transient increase in the c-Rel level in the nucleus, normalization of the NF-κB-DNA binding activity, and downregulation of the NF-κB-regulated genes. Our results provide new insights into the statin-mediated neuroprotective action against stroke based on NF-κB pathway inhibition.

The influence of gradually increasing the concentration of desflurane on cerebral perfusion pressure in rabbit.

BACKGROUND: In nearly all cases of general anaesthesia with a volatile agent, the anaesthetic concentration has to be increased. Since the anaesthetic affects both the factors determining intracranial homeostasis and the systemic circulation, it is crucial that cerebral perfusion pressure (CPP) is protected. The aim of the present study was to assess the influence of gradually increased concentrations of desflurane on the cerebral and systemic circulations based on CPP, mean arterial pressure (MAP), intracranial pressure (ICP) and their correlations. METHODS: The study was carried out on 25 rabbits of the same gender (male) randomly assigned to two groups: control (n = 10) and group I (n = 15). Over three 15-minute periods, the animals were exposed to increase concentrations of desflurane so as to achieve 1/3, 2/3 and 1 MAC Minimal Alveolar Concentration (3, 6, 9 vol%) of the effective end-tidal concentration of desflurane (Et) at the end of each period, respectively. RESULTS: Intragroup analysis of CPP changes demonstrated decreases in its successive values from minute 18, compared with baseline values. The mean values of ICP did not differ throughout the experiment. From minute 19 on, all successive values of MAP decreased compared with baseline values. A weak correlation (r = -0.2179) was found between ICP and CPP and a strong correlation between MAP and CPP (r = 0.98829). Moreover, there was a strong correlation between Etdesflurane vs. CPP (r = -0.8769) and MAP (r = -0.8224) and a weak correlation versus ICP (r = 0.15755). CONCLUSIONS: A decrease in CPP induced by desflurane was associated with a decrease in MAP but not an increase in ICP. The depressive effect of desflurane on the cerebral and systemic circulations is a consequence of its effector site concentration.

The influence of propofol on middle cerebral artery flow velocity (VMCA) in patients with unruptured intracranial aneurysms during induction of general anaesthesia.

BACKGROUND: The estimated prevalence of unruptured intracranial aneurysms is 3%. Standard monitoring does not enable one to assess the influence of anaesthetics on the factors determining intracranial homeostasis. Thanks to transcranial Doppler ultrasonography, middle cerebral artery flow velocity (VMCA), reflecting cerebral blood flow, can be measured. The aim of the study was to assess the effects of propofol on intracranial homeostasis in patients with unruptured intracranial aneurysms during the induction of anaesthesia based on VMCA changes. METHODS: The study encompassed 21 patients (group II) anaesthetised for elective craniotomy due to unruptured intracranial aneurysms. The control group (group I) included 21 patients who underwent discoidectomy. VMCA, as well as HR, MAP, etCO2, and SpO2 were monitored at the following time points: T0 ­ onset of study; T1 ­ after 1 minute; T2 ­ onset of preoxygenation; T3 ­ after 1 minute of preoxygenation; T4 ­ administration of fentanyl; T5 ­ 1 minute after fentanyl; T6 ­ administration of propofol; T7 ­ 1 minute after propofol; T8 ­ intubation; T9 ­ 1 minute after intubation; T10 ­ 2 minutes after intubation. RESULTS: In both groups, no changes in mean HR, etCO2 and SpO2 were observed at the successive time points of observation. In groups I and II, an MAP decrease between T6 and T7 and an MAP increase between T7 and T9 were noted. There were no intergroup differences in mean values of MAP at the times of observation. In both groups and bilaterally, a VMCA decrease was recorded between T6 and T7 and an increase between T7 and T8. There were no intergroup differences in mean values of VMCA at the times of observation. In both groups, a weak correlation between VMCA and MAP changes was found bilaterally. CONCLUSIONS: Propofol depresses the cerebral circulation during the induction of anaesthesia. The presence of an unruptured aneurysm does not affect the reactivity of the cerebral vessels during the induction of anaesthesia with propofol.

Molecular mechanisms of bacterial infections of the central nervous system.

Central nervous system (CNS) infections may involve the meninges, brain and/or spinal cord. The most common etiologic agents are Streptococcus pneumoniae, group B Streptococci, Neisseria meningitidis, Haemophilus influenzae, and Listeria monocytogenes. CNS is characterized by specific structure and function. Despite a unique system of brain barriers and autonomous immune system, CNS is very susceptible to microorganisms which may invade directly, via the blood, or less frequently by reverse axonal transport. The complex process of bacteria and activated polymorphonuclear leukocyte transfer to the subarachnoid space, which is devoid of natural immune defence mechanisms, initiates an inflammatory response that subsequently spreads to the brain tissue. Consequences of these changes include damage to the blood-brain barrier, development of vasogenic cerebral oedema, and intracranial pressurevolume disturbances leading to impaired CNS perfusion.

The use of sugammadex for the reversal of vecuronium-induced neuromuscular block following intracranial surgery.

BACKGROUND: Total intravenous anaesthesia with propofol and remifentanil is widely used in neuroanaesthesiology and enables the quick recovery and early neurological assessment of patients. The administration of muscle relaxants carries a risk of residual relaxation following surgery. The administration of a suitable dose of sugammadex reverses the neuromuscular block irrespective of its depth and has none of the side effects associated with acetylcholinesterase inhibitors. The aim of the present study was to evaluate the usefulness of sugammadex for the reversal of vecuronium-induced effects following intracranial surgery. METHODS: The study involved 38 women who underwent supratentorial tumour removal. These women were randomly divided into two groups. Total intravenous anaesthesia with propofol and remifentanil using target-controlled infusion was administered according to the Schnider and Minto models, respectively. Endotracheal intubation was performed after the target concentrations of propofol and remifentanil reached 4 µg mL⁻¹ and 4 ng mL⁻¹, respectively. Vecuronium (100 µg kg⁻¹) was administered, and no response to TOF stimulation was observed. Relaxation was continued via the continuous infusion of vecuronium (0.8-1.2 µg kg⁻¹ min⁻¹) to provide a TOF of 2 throughout the surgery. In group I, neuromuscular conduction was restored with intravenous sugammadex (2 mg kg⁻¹), whereas in group II, no reversal agents were administered. RESULTS: The times of the return of spontaneous breathing, extubation, eye opening (both spontaneous and in response to a verbal command) were found to be longer in group II than group I. CONCLUSION: The use of sugammadex following craniotomy accelerates the achievement of optimal extubation conditions.

The effect of bispectral index monitoring on anaesthetic requirements in target-controlled infusion for lumbar microdiscectomy.

BACKGROUND: Target-controlled infusion (TCI) is used to maintain the desired concentration of a hypnotic drug in the plasma and brain. However, pharmacodynamic variability can cause problems with maintaining the adequate level of anaesthesia. The bispectral index (BIS) is one of only a few parameters that allow an assessment of the depth of anaesthesia. In the present study, we attempted to determine the optimal dosages of drugs used for total intravenous anaesthesia with TCI based on BIS-guided monitoring of depth of anaesthesia. METHODS: The study was conducted in 60 ASA I patients undergoing elective surgery due to lumbar discopathy. The participants were divided into two groups of 30 individuals. The patients were premedicated with 15 mg oral midazolam. Group I was the control group; group II received BIS monitoring. Anaesthesia was induced with TCI propofol (4 mg mL⁻¹), fentanyl (2 mg kg⁻¹) and vecuronium (0.12 mg kg⁻¹) and maintained with TCI propofol, continuous infusion of vecuronium (0.03 mg kg⁻¹ h⁻¹) and fractionated doses of fentanyl. ECG, HR, MAP, SaO2, ETCO2, and the degree of neuromuscular blockade were monitored, specifically at the following time points: T1 - before induction, T2 - after induction, T3 - after intubation, T4 - after positioning of the patient, T5-T13 - every 5 min during surgery, T14 - on completion of surgery, T15 - before extubation, T16 - after extubation. RESULTS: The study groups were comparable in terms of age, body weight, duration of anaesthesia and recovery time. The haemodynamic parameters, such as HR and MAP, did not differ significantly between the groups. In both groups, changes in the mean MAP values were observed between T1 and T2, T2 and T3, T3 and T4 as well as T14and T15. The total dose of fentanyl and the doses of propofol were lower in the group that received BIS monitoring. CONCLUSION: BIS monitoring reduces the doses of opioids and hypnotics used during total intravenous anaesthesia by TCI.

Transcription factor Pax6 is expressed by astroglia after transient brain ischemia in the rat model.

Reactive astrogliosis is regarded as an universal astrocytic response to different kinds of lesions, concerned with glial fibrillary acidic protein (GFAP) up-regulation, cellular hypertrophy and proliferation. The origin of reactive and proliferating cells in the adult brain is still disputable. Persistent progenitors as well as de-differentiating adult cells of various glial lineages are regarded as possible candidates. Pax6 transcription factor is one of the characteristic markers of astroglial de-differentiation, also important for regulation of neural and glial proliferation. Various kinds of pathological stimuli evoke reactive response, differentiated in its morphological, biochemical and immunological character. The aim of this study was to assess the dynamics of astroglial morphological and proliferative response to ischemic injury. One-hour transient focal cerebral ischemia was applied to evoke the reactive astrogliosis in twenty five adult male Wistar rats. The astrocytic morphological and proliferative reactions to ischemia were studied in the period of 6 weeks by means of GFAP and Pax6 immunofluorescent staining. A strong reactive astroglial response was observed in the cerebral cortex and striatum, manifested by GFAP and Pax6 up-regulation and astrocytic hypertrophy. Apparent morphological changes appeared within 24 hrs after ischemia. The GFAP/Pax6 colocalization was numerous and observed 24 hrs after ischemia. A characteristic spatial distribution of GFAP/Pax6 double-labelled astrocytes and Pax6 single-labelled nuclei was revealed, with the latter situated more distantly from the ischemic core. The maximal intensity of astrocytic reaction was present from the first post-ischemic week. Astroglial hypertrophic changes and proliferative reaction were more intense in the striatum than in the cerebral cortex. Our observations reveal intensive astroglial de-differentiation and proliferative response, reflected by dynamic Pax6 up-regulation within GFAP-immunoreactive astrocytes. Transient cerebral ischemia evokes strong reactive astrogliosis, which is apparently differentiated in respect to the post-ischemic period and particular brain structure.

Anaesthetic management for endovascular treatment of unruptured intracranial aneurysms.

BACKGROUND: Endovascular techniques for treatment of intracranial aneurysms are increasingly commonly applied. In general, the procedures are short, require general anaesthesia and complete immobilisation of patients. The aim of the present study was to assess the usefulness of general anaesthesia with propofol and laryngeal mask airway for endovascular management of intracranial aneurysms based on analysis of haemodynamic stability. METHODS: The study encompassed 26 patients undergoing endovascular treatment of intracranial aneurysms. The mean arterial pressure (MAP), heart rate (HR), bispectral index (BIS), end-tidal CO2(E(T)CO2) and haemoglobin saturation with oxygen (SpO2 ) were determined at eight measurement points: T1 - before anaesthesia induction, T2 - after induction, T3 - after LMA insertion, T4 - during arteriography, T5 - during "coiling" , T6 - at completion of propofol infusion, T7 - before LMA removal, T8 - after LMA removal. RESULTS: MAP and HR were found significantly reduced between T2 and T1 . To maintain BIS within the range of 40-60, the following propofol infusion rates (in mg kg b.w.⁻¹ h⁻¹ ) were required: T2 - 4.5 ± 0.3; T3 - 4.6 ± 0.7; T4 - 4.5 ± 0.8 and T5 - 4.4 ± 0.6. E T CO2 and SpO2 were not demonstrated to be changed. The mean duration of anaesthesia and of recovery was 64.3 ± 21.8 and 8.9 ± 4.8 min, respectively. CONCLUSIONS: General anaesthesia with propofol and LMA ensures suitable conditions for endovascular treatment of intracranial aneurysms.

Complications after using the Airtraq laryngoscope for a predicted difficult intubation.

Although standard management of an expected difficult intubation is based on fibre-optic techniques, the application of optical laryngoscopes such as Airtraq is gaining widespread acceptance. We here describe a case where an intubation attempt with the Airtraq laryngoscope was not only unsuccessful, but negatively influenced subsequent use of a flexible fibroscopic approach.

Effect of sevoflurane on cerebral perfusion pressure in patients with internal hydrocephalus.

BACKGROUND: Due to its confirmed neuroprotective properties, sevoflurane is one of a few anaesthetics used for neuroanaesthesia. Its effects on the cerebral and systemic circulations may be of particular importance in patientswith intracranial pathology. This study aimed to evaluate the effect of sevoflurane at concentrations lower than 1 MAC on cerebral perfusion pressure (CPP) in patients with internal hydrocephalus. METHODS: The study was conducted on14 patients with internal hydrocephalus, who underwent ventriculo-peritoneal shunt implantation. After inserting the catheter into the lateral cerebral ventricle, sevoflurane, at 1.1 and 2.2 vol%, was initiated at two successive 15-minute intervals. The intracranial pressure (ICP) was continuously measured; special attention was focused on the values prior to and at the end of each observation period. The following parameters were monitored: mean arterial pressure (MAP), CPP, heart rate, end-tidal CO2 concentration, core body temperature, and the inspiratory and end-expiratory concentrations of sevoflurane. RESULTS: The HR and MAP decreased during successive observation intervals compared to baseline values. Likewise, the CPP decreased from 75.6 ± 2.8 mm Hg to 72.2 ± 2.6 mm Hg to 70.2 ± 0.8 mm Hg. The baseline value for ICP was 16.3 ± 0.6 mm Hg and increased to 17.7 ± 0.8 and 18.9 ± 0.5 mm Hg during the next observation periods. CONCLUSIONS: Sevoflurane administered ata concentration below 1MAC to patients with internal hydrocephalus increases the ICP and decreases the MAP, which leads to adecrease in CPP. The CPP decrease is more dependent on depressing the systemic circulatory system than an increased ICP.

Comparison of target controlled infusion and total intravenous anaesthesia with propofol and remifentanil for lumbar microdiscectomy.

BACKGROUND: Propofol is often combined with remifentanil for induction and maintenance of total intravenous anaesthesia. Target-controlled infusion (TCI) permits adapting infusion to pharmacokinetic models. In this study we compared depth of anaesthesia, haemodynamic variables and times to recovery in patients scheduled for lumbar microdiscectomy and receiving either manually controlled (group I) or target- controlled (group II) infusion of propofol and remifentanil for anaesthesia. METHODS: Twenty three patients (group I) received a bolus induction of propofol 2 mg kg(-1) and remifentanil 1 µg kg(-1). Twenty five patients (group II) received propofol and remifentanil at an initial effect site concentration of 4 µg mL(1) and 4 ng mL(-1) respectively. According to BIS and haemodynamics, propofol/remifentanil infusion rates (group I) or concentration of propofol/remifentanil at an effect-site were adjusted upwards or downwards. We monitored bispectral index (BIS), mean arterial pressure (MAP) and heart rate (HR) during subsequent stages of anaesthesia and operation (T1-T10). RESULTS: Induction and total doses of propofol and remifentanil, times to recovery were comparable in both groups. BIS was lower at T2-T10 in comparison to baseline values. At T4 and T5 BIS was lower in group II than in group I. In group I, mean HR values were lower at T7-T9 in comparison to baseline values. In exeption of MAP at T6 in group II, MAP was lower at T2-T9 in comparison to baseline values in both groups. CONCLUSION: There are no clinically important differences in haemodynamic variables, depth of anaesthesia, time to recovery and doses of propofol/remifentanil between manually controlled and target-controlled infusion of propofol and remifentanil.

Iliac artery injury during lumbar microdiscectomy.

BACKGROUND: Accidental laceration of major abdominal vessels during lumbar disc surgery is a relatively rare complication that requires rapid diagnosis and management. CASE REPORT: A 25-yr-old woman, operated on for an L4-L5 disc hernia, developed cardiovascular collapse after disc removal. This was treated with volume replacement and ephedrine, and a postoperative CT scan revealed a large retroperitoneal haematoma. During an immediate laparotomy, a 10 cm laceration of the left iliac artery was repaired and massive blood loss replaced (to lowest haemoglobin concentration during the surgery was 2.1 mmol L(-1)).The patient made a full recovery. CONCLUSION: In any case of unexpected hypotension during lumbar disc herniation surgery, accidental vascular damage should be suspected and a CT scan performed immediately.

[Neuromuscular block monitoring for optimisation of conditions for endotracheal intubation]. / Monitorowanie bloku nerwowo-miesniowego wywolanego cisatrakurium podczas indukcj znieczulenia ogólnego.

BACKGROUND: The choice of an appropriate moment for endotracheal intubation is essential to avoid serious motor and cardiovascular reactions during laryngoscopy and tube insertion.The purpose of the study was to compare the effects of intubation on laryngoscopy conditions and cardiovascular response, when choice of the moment for intubation was directed by either clinical or train-of-four assessment. METHODS: Adult ASA I patients, scheduled for lumbar disc hernia surgery, who received 0.15 mg kg(-1) of cis-atracurium for muscle relaxation, were divided in two groups. Patients in group I were intubated when the attending anaesthesiologist assessed muscle relaxation to be adequate. Patients in group II were intubated when there was no visual response to train-of-four stimulation of the ulnar nerve. RESULTS: Forty-five patients were enrolled in the study. The mean time for intubation was 162.3+/-35 sec in group I and 339.3+/-73.7 sec in group II. Adequate and excellent conditions for intubation were achieved in all patients of group II, compared to only 53% of patients in group I. Heart rate and arterial blood pressure immediately after intubation were significantly lower (p<0.001) in group II. CONCLUSION: The objective assessment of neuromuscular relaxation priorto endotracheal intubation provides better conditions and minimization of cardiovascular reaction.

The molecular mechanisms of cell death in the course of transient ischemia are differentiated in evolutionary distinguished brain structures.

There is large body of evidence suggesting distinct susceptibility to ischemia in various brain regions. However, the reason for this remains unexplained. Comparative studies of programmed cell death (PCD) pathways indicate their differentiated evolutional origin. The caspase-independent pathway is regarded as an older, whereas the caspase-dependent--as more advanced. In our study we address the question of whether there are any characteristic differences in the activation and course of PCD in phylogenetically and morphologically distinguished brain structures after transient focal ischemia. Using Western blot, we studied changes in expression of caspases: 3, 8, 9, and AIF in the frontoparietal neocortex, archicortex (CA1 and CA2 sectors of the hippocampus) and striatum, during reperfusion after 1 h occlusion of the middle cerebral artery. The caspase and AIF expression were differentiated between the studied structures. The activation of only the caspase-dependent pathway was observed in the neocortex. In the archicortex and striatum both caspase-dependent and caspase-independent pathways were activated, although in the latter the extrinsic apoptotic pathway was not activated. In summary, it is conceivable that structures of different evolutionary origin undergo cell-death processes with the participation of phylogenetically distinguished mechanisms. The previously reported unequal susceptibility to ischemia may co-exist with activation of different cell death pathways.

Percutaneous tracheostomy in patients with disorders of the central nervous system.

BACKGROUND AND PURPOSE: Patients with disorders of the central nervous system frequently require maintenance of an artificial airway due to impairment of the cough reflex and swallowing, or due to the necessity to apply long-term mechanical ventilation. The technique of percutaneous tracheostomy, introduced in recent years to clinical practice globally, enables tracheostomy and establishment of an artificial airway in a bedside setting, in a quick, simple and minimally traumatic manner. It does not require the operating theatre environment and is associated with lower complication rates than the traditional surgical technique. MATERIAL AND METHODS: In the period from March 2003 till February 2007, we performed 75 procedures of Griggs mode percutaneous tracheostomy in intravenous anaesthesia, with use of a disposable Percutaneous Tracheostomy Kit (SIMS Portex, UK). The group of patients comprised 36 women and 39 men. Mean patient age was 57.4+/-17.9 years. RESULTS: On average, the procedure was performed on the 8th (7.8+/-2.6) day after intubation, and its average duration was 6.0+/-3.3 minutes. The most frequent complication was local bleeding from the site (13%), most of which, however, regressed spontaneously. Also observed were: puncture of the tracheal tube sealing cuff (7%), damage to the isthmus of the thyroid (3%), and extratracheal positioning of the tracheal tube (3%). In all the cases the procedure was concluded successfully. CONCLUSIONS: Griggs mode is a simple and safe technique enabling percutaneous tracheostomy in patients with pathology of the central nervous system. However, further research is needed to evaluate potential delayed complications of the procedure.

The effect of propofol on astro- and microglial reactivity in the course of experimental intracerebral haemorrhage in rats.

The glial cells play an important role in pathophysiology of the intracerebral haemorrhage (ICH). Thus the attempt at evaluating the possible influence of the propofol on the reactivity of astro- and microglial cells in the course of ICH was performed. 50 rats were divided into two groups depending on the applied anaesthesia. All animals were generally anaesthetized with fentanyl, dehydrobenzperidol and midazolam. No additional agents were given to the animals of the control group (group I). In the experimental group (group II), the animals received additionally intraperitoneally propofol in a dose of 50 mg/kg every thirty minutes. ICH was produced through infusion of the blood into the striatum. The astrocytic and microglial cells population was assessed on the 1, 3, 7, 14 and 21 days after producing a haematoma using antibodies anti-GFAP and OX42. The stereological analysis was applied to estimate the numerical density of immunoreactive cells and the distribution of their types. On the 14th and 21st days of observation the density of GFAP-immunoreactivity (ir) cells was significantly higher in group II than that in group I. There were no differences in percentage distribution of GFAP-ir astrocytes between group I and group II. On the 3rd, 14th and 21st days of observation the density of OX42-ir cells was higher in group II in comparison with group I. For the 7th, and 21st days of survival the percentage of the ameboid form of OX42-ir cells was significantly lower in group I than that in group II. The administration of propofol during anaesthesia in the animals with ICH has evoked an increase of the activation of the astro- and microglial cells.

Evolution of microglial and astroglial response during experimental intracerebral haemorrhage in the rat.

Intracerebral haemorrhage is a strong stimulus for both microglial and astroglial activations. There are some important pathophysiological features during haemorrhage that do not occur in ischaemic or traumatic brain injuries, and may influence the dynamics and intensity of glial activation. Studies on the evolution of glial reaction may have practical importance to the introduction of new therapeutic methods for influencing the inflammatory reaction during haemorrhage. Microglial and astroglial responses to experimental intracerebral haematoma were studied in 50 adult rats for 5 minutes after injection of 100 microl autologous arterial blood into the striatum. The survival period varied from 1 to 21 days. Microglial-macrophage lineage cells were immunocytochemically stained with antibodies OX42, OX6 and ED1. The astrocytic population was studied by means of anti-GFAP staining. Changes in cellular morphology and intensity of staining were time-dependent reactions in both microglial and astroglial cells. Strong activation of microglial-macrophage lineage cells revealed with OX6-and OX42-immunoreactivity started during the first postoperative day. The complete pattern of activation for ED1-immunoreactivity was observed from the third postoperative day. At this stage, numerous phagocytic macrophages started to appear in the perihaematoma region. Morphological changes were most intensive during the second postoperative week. The astroglial (anti-GFAP) reaction was observed after the third postoperative day and proceeded less dynamically. The glial reaction gradually stopped but not completely during the period of observation. The early occurrence of glial activation, pattern of morphological changes and characteristic sequence of antigens expression indicate a very intense type of glial reaction. Evolution of glial response to haemorrhage reveals characteristic features. In our opinion, the initial phase of glial activation, comprising 72 hours after the occurrence of haemorrhage, is potentially the most promising period for influencing the extent of glial reaction with therapeutic agents.