Nicotine-induced NO-mediated increase in cortical cerebral blood flow is blocked by beta2-adrenoceptor antagonists in the anesthetized rats

Involvement of nitric oxide (NO) and beta-adrenoceptors in an increase in the cortical cerebral blood flow (CBF) following an intravenous (i.v.) injection of a small dose of nicotine which did not affect the systemic blood pressure in the rats was investigated. I.v. injection of nicotine (30 microg/kg) for 1 min produced a significant increase in CBF lasting for more than 20 min without a significant effect on the systemic blood pressure. I.v. injection of L-N(G)-nitroarginine methylester (30 mg/kg) significantly attenuated nicotine-induced increase in the cortical CBF. The attenuation was reversed by i.v. injection of L-arginine (300 mg/kg), suggesting an intimate role of nitric oxide (NO) in nicotine-induced increase in the cortical CBF. The nicotine-induced increase in the cortical CBF was significantly attenuated by propranolol (10 mg/kg, i.v.) and ICI 118,551 (a beta2-adrenoceptor antagonist, 10 mg/kg, i.v.) but not by metoprolol (a beta1-adrenoceptor antagonist, 10 mg/kg, i.v.). Beta2-adrenoceptors on presynaptic nitrergic nerves may be involved in nicotine-induced NO-mediated increase in the cortical CBF.     

Extraction of [99mTc]-d,l-HM-PAO across the blood-brain barrier

The initial extraction (E) across the blood-brain barrier (BBB) of [99mTc]-d,l-HM-PAO after intracarotid injection was measured in 14 Wistar rats and 6 patients using the double indicator, single injection method with Na-24 as the cotracer. In both series, cerebral blood flow (CBF) was measured using the initial slope of the xenon-133 washout curve after intracarotid bolus injection. In rats, bolus size (20 or 120 microliters), bolus type (saline or 10% albumin), or CBF were changed. First-pass extraction was dependent on CBF (p less than 0.001): With a small bolus of saline and at resting CBF (0.75 ml/g/min), E was 0.81, decreasing to 0.56 at a high CBF (1.5 ml/g/min). The calculated permeability surface area product (PS) increased linearly from 1.2 to 1.5 ml/g/min when CBF increased from 0.8 to 1.5 ml/g/min (p less than 0.01). E was found to increase when the bolus volume of saline was increased from 20 to 120 microliters, while using a 120 microliters bolus containing 10% albumin resulted in a decrease in E. This suggests that HM-PAO binding to albumin is not totally and rapidly reversible during a single passage through brain capillaries and that binding to blood elements may reduce the apparent extraction across brain capillaries. In patients using a bolus of 1 ml saline, E decreased linearly with increasing CBF (r = -0.81, p less than 0.001). For a CBF of 0.59 ml/g/min and an average apparent E of 0.72, an apparent PS product of 0.76 ml/g/min was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebrovascular responses to pathophysiological insult in diabetic rats.

Diabetes mellitus is associated with altered cerebrovascular responsiveness and this could contribute to the pathology of stroke in diabetic patients. In these studies, we used a model of haemorrhagic stroke (intrastriatal injection of 50 microl blood) to examine subacute perilesional perfusion and blood-brain barrier (BBB) integrity in spontaneously diabetic rats. Volumes of striatal oligaemia (blood flow < 35 ml 100 g(-1) min(-1)) were significantly increased (>300%) in diabetic rats with intrastriatal blood, compared to either non-diabetic rats with blood or control diabetic rats with striatal injection of silicon oil. However, the increase in BBB permeability was both qualitatively and quantitatively similar in diabetic and control rats. Poorer outcomes following haemorrhagic stroke in diabetic patients may thus result from dysfunctional cerebrovascular control, and particularly decreased dilatatory reserve.     

A comparison of cerebral blood flow during basal, hypotensive, hypoxic and hypercapnic conditions between normal and streptozotocin diabetic rats

This study was undertaken to determine the differences (if any) in cerebral blood flow (CBF) between streptozotocin (STZ) diabetic and normal rats. CBF was studied in connection with episodes of hypoxia, hypercapnia and hypotension as compared to the basal condition. Overall basal CBF rates in streptozotocin diabetic rats were significantly higher than in normal animals. However, initial basal flow rates prior to the first challenge were insignificantly higher in the STZ diabetic group. The higher CBF rate in STZ diabetics was also seen during the peak flows of the hypoxic and hypercapnic challenges. Furthermore, although overall CBF decreased for both the normal and STZ diabetic groups during hypotension, higher CBFs were observed in the STZ diabetic group during this challenge. The percent increase in CBF above control resulting from hypoxia or hypercapnia and the changes in CBF resulting from hypotension were not significantly different in the STZ diabetic and normal groups. The results indicate that the STZ diabetic rat regulates CBF in the same manner as the normal rat in response to hypoxia, hypercapnia and hypertension. The STZ diabetic rat executes these CBF responses at a slightly higher CBF rate. In view of the finding that the regulation of CBF is unaltered in the STZ diabetic animal, it is hypothesized that the associated hyperglycemia may be the causative agent for the cerebral ischemic susceptibility associated with long-term diabetes mellitus rather than a failure of CBF regulation.     

Fibrinolysis and aspiration of experimental intracerebral hematoma reduces the volume of ischemic brain in rats.

The hypothesis was tested in rats that brain ischemia by an intracerebral hematoma can be ameliorated by fibrinolysis and aspiration of the hematoma. Intraparenchymal blood clots were generated by the injection of 50 microliters of autologous blood into the right caudate nucleus in two portions seven minutes apart. Thirty or 120 min later 12 microliters recombinant tissue plasminogen activator (rtPA) or 0.9% NaCl were injected and after 30 min the resolved hematoma was aspirated. Six hours later cerebral blood flow (CBF) was determined by 14C-iodoantipyrine autoradiography. Tissue volumes of CBF < 10 ml 100 g-1 min-1 and CBF < 30 ml g-1 min-1 were determined. Clot and lesion volume were quantified histologically from serial sections stained for succinate-dehydrogenase (SDH) activity. In rtPA-treated rats the major part of the hematoma could be evacuated 30 min as well as 120 min after production of the clot. The volume of ischemic brain (CBF < 10) was significantly reduced (p < 0.05) in the rtPA group compared to saline-treated and control groups irrespective of the time of treatment. In contrast, no difference was found between the control group and the experimental groups when the volumes of brain tissue surrounding the lesion were compared which had values of CBF < 30 ml 100 g-1 min-1. In a rat model of intracerebral hemorrhage, treatment by local fibrinolysis followed by aspiration of the hematoma is effective in reducing the volume of ischemic brain tissue and of the remaining clot volume.     

A New Technology for Detecting Cerebral Blood Flow: A Comparative Study of Ultrasound Tagged NIRS and 133Xe-SPECT

There is a need for real-time non-invasive, continuous monitoring of cerebral blood flow (CBF) during surgery, in intensive care units and clinical research. We investigated a new non-invasive hybrid technology employing ultrasound tagged near infrared spectroscopy (UT-NIRS) that may estimate changes in CBF using a cerebral blood flow index (CFI). Changes over time for UT-NIRS CFI and 133Xenon single photon emission computer tomography (133Xe-SPECT) CBF data were assessed in 10 healthy volunteers after an intravenous bolus of acetazolamide. UT-NIRS CFI was measured continuously and SPECT CBF was measured at baseline, 15 and 60 min after acetazolamide. We found significant changes over time in CFI by UT-NIRS and CBF by SPECT after acetazolamide (P ≤ 0.001). Post hoc tests showed a significant increase in CFI (P = 0.011) and SPECT CBF (P < 0.001) at 15 min after acetazolamide injection. There was a significant correlation between CFI and SPECT CBF values (r = 0.67 and P ≤ 0.033) at 15 min, but not at 60 min (P ≥ 0.777). UT-NIRS detected an increase in CFI following an acetazolamide bolus, which correlated with CBF measured with 133Xe-SPECT. This study demonstrates that UT-NIRS technology may be a promising new technique for non-invasive and real-time bedside CBF monitoring.     

Nicardipine increases cerebral blood flow but does not improve neurologic recovery in a canine model of complete cerebral ischemia

The effects of the calcium entry blocker nicardipine on CBF, CMRO2, and neurologic outcome following 10 min of complete cerebral ischemia were examined in dogs. In CBF and CMRO2 studies, the CBF in the untreated group (seven dogs) and the nicardipine group (seven dogs; 20 micrograms kg-1 at 30 min postischemia and a subsequent infusion of 2 micrograms kg-1 min-1 for 90 min) initially increased to 300-400% and then returned to preischemic values at 30 min postischemia. Thereafter the CBF in the untreated group significantly decreased to 50% of preischemic values for the following 90-min period (hypoperfusion), while the CBF in the nicardipine group did not differ from preischemic values. The CMRO2 in both groups decreased to approximately 50-80% of preischemic values after 15 min postischemia and did not differ between the groups throughout the study. In neurologic outcome studies, 18 dogs were divided into three groups (of six dogs each): untreated; saline infusion only, posttreated; nicardipine as in CBF and CMRO2 studies, pretreated; nicardipine 20 micrograms kg-1 at 2 min preischemia and a subsequent infusion of 2 micrograms kg-1 min-1 from immediately postischemia to 120 min postischemia. Nicardipine treatment initiated either before or after ischemia failed to improve neurologic outcome at 48 h postischemia. Thus, the increase of postischemic global CBF by nicardipine is not accompanied by neurologic recovery in a canine model of complete cerebral ischemia.     

Regional cerebral blood flow during spreading cortical depression in conscious rats

Spreading cortical depression (SCD) of EEG activity was induced in one cerebral hemisphere of conscious restrained rats by direct current stimulation of the lateral frontal cortex. Regional CBF was measured using [14C]iodoantipyrine and brain dissection. An early phase of increased CBF was not measured in conscious rats, but an early relative hyperperfusion was measured if the resting CBF was first reduced by treatment with pentobarbital or indomethacin. A long-lasting reduction in CBF was measured in conscious rats following the passage of SCD. This flow reduction resolved after 3 h. In conscious rats, CBF decreased in the striatum and thalamus ipsilateral to the SCD, paralleling the CBF changes occurring in the cortex. The CBF change in these deep structures was abolished by pentobarbital. An early transient increase in regional CBF was measured in the cerebral cortex contralateral to the hemisphere involved with SCD in conscious rats. This early contralateral hyperperfusion was also abolished by pentobarbital or indomethacin but not by atropine or propranolol. The vascular response to SCD in conscious rats differs from that which occurs in anesthetized rats.     

Somatosensory evoked potentials in cerebral ischemia of rabbits

Twenty-one rabbits were used in the ischemic group and six in the control group. Cerebral ischemia of variable degree was induced by Fe particle injection method. Somatosensory evoked potentials (SEPs) and cerebral blood flow (CBF) were compared when the CBF levels decreased to their minimum. The latency of the SEPs increased along with the decrease of the CBF when it was lower than 20 ml/100 g/min (68% of the pre-ischemic control level). This may be related to the ischemic change of the white matter. The amplitude showed diphasic changes. When the CBF decreased below 20 ml/100 g/min, the amplitude increased; when the CBF was lower than 11 ml/100 g/min (38% of the pre-ischemic level), it decreased. These results indicate that the functions of the cerebral cortex might be excited in mild ischemia, and be suppressed in severe ischemia.     

Persistence of Impaired Autoregulation of Cerebral Blood Flow in the Postictal Period in Piglets

Cerebral blood flow (CBF) autoregulation was evaluated in the postictal period in unanesthetized term newborn piglets with a mean age of 5.7 +/- 3 days. Seven animals (group 1) received 1 mg/kg bicuculline to induce brief generalized seizures, and six control animals (group II) received saline. Twenty to 90 min after the end of seizure activity in group I or saline injection in group II, CBF was measured by the radioactive labeled microspheres method at three levels of mean arterial blood pressure (MABP) obtained by controlled blood withdrawal within the normal range for autoregulation. In the postictal period, baseline CBF was higher in group I than in group II (85 +/- 21 vs. 48 +/- 7 ml/min/100 g, p less than 0.001). During hypotension, total CBF was positively correlated with variations of MABP in group I (r = 0.739, p less than 0.01) but not in group II. Regional CBF showed the same correlation with MABP. These data show that after seizures in piglets, the rise in CBF is associated with a persistent impairment of CBF autoregulation. These hemodynamic alterations may be relevant in the pathogenesis of hemorrhagic or ischemic brain lesions.     

Haloperidol and oestrogens induce c-myc and c-fos expression in the anterior pituitary gland of the rat

Abstract

Decreased dopaminergic and increased oestrogenic effects induce prolactin release and DNA synthesis in prolactin secreting cells of the adult male rats. Oestrogen treatment for 7 days significantly increased the levels of prolactin, c-myc and c-fos mRNAs. The effect of oestrogens was reversed by the administration of the dopaminergic agonist bromocriptine. There was an early gradual increase of c-myc mRNA levels beginning 30 min after the injection of the steroid, c-fos mRNA levels increased sharply 15 min after oestrogen administration and decreased to basal values 15 min later to remain at this level over the period of time evaluated. Administration of the dopaminergic antagonist haloperidol did not change the levels of protooncogenes mRNA. However, in rats previously treated with oestrogens for 7 days c-myc mRNA levels increased 90 min after the injection of haloperidol and decreased to basal values after 2.5 h. c-fos mRNA levels increased sharply 30 min after haloperidol administration and also decreased to basal values 1 h later. We propose that changes in protooncogenes expression may be involved in the stimulation of cell proliferation induced by prolactin secretion. [Neurol Res 1993; 15: 339-343]     

Hemodynamic consequences of common carotid artery thrombosis and thrombogenically activated blood in rats

We documented the hemodynamic consequences of nonocclusive common carotid artery thrombosis (CCAT) and tested the hypothesis that vasoactive substances capable of altering local CBF (LCBF) are released into the systemic circulation following cerebrovascular injury. Ten minutes after photochemically induced CCAT, an autoradiographic determination of LCBF was conducted with [14C]iodoantipyrine. In blood transfusion studies using donor and recipient rats, a 1-ml sample of thrombogenically activated blood (TAB) collected downstream from the forming thrombus was reinjected into a recipient rat 15 or 60 min before CBF study. A heterogeneous pattern of abnormal LCBF was documented in the ipsilateral hemisphere of CCAT rats and recipient rats receiving TAB 15 min before CBF study. Acute hemodynamic abnormalities included ischemic (less than 35% of control) and hyperemic (greater than 125% of control) foci and more global reductions (50-80% of control) in cortical and subcortical LCBF. Border zone hyperemia exceeding 2.0 ml/g/min was associated with focal sites of severe LCBF reductions. Although recipient rats that received TAB 15 min before CBF study displayed similar hemodynamic abnormalities, LCBF values in 60-min recipient rats were not significantly different from control despite ischemic foci. Humoral factors generated during CCAT appear to be responsible for the acute LCBF consequences of cerebrovascular thrombosis. Vasoactive substances released from a thrombotic site, capable of regionally affecting vascular reactivity in a time-dependent fashion, might be expected to participate in the pathogenesis of transient ischemic attacks and acute stroke.     

Measurement of somatosensory evoked potential in the Mongolian gerbil: the effects of cerebral ischaemia

Normal somatosensory evoked potential (SEP) as well as changes after incomplete cerebral ischaemia following bilateral carotid artery occlusion (BCO) were characterized in the Mongolian gerbil. BCO significantly decreased cerebral blood flow (CBF). Reperfusion CBF at 10 min and 2, 3 and 4 h was significantly below preischaemic control values. BCO decreased SEP amplitude but had no effect on EP-P3 central conduction time. BCO did significantly increase EP-P11 central conduction time. Reperfusion amplitudes at 10 min and 2, 3 and 4 h revealed a significant increase only at 4 h when compared to the ischaemic amplitude. EP-P11 central conduction time at 10 min reperfusion showed dramatic improvement compared to ischaemic values, although values at 2, 3 and 4 h reperfusion were not statistically different from ischaemic values. A separate group of animals prepared identically but without BCO showed no significant changes in either SEP or CBF over time. These studies establish the protocol necessary to measure SEP in the Mongolian gerbil. In the future SEP may be used as an integral tool in the study of the primary determinants of neurophysiological recovery following cerebral ischaemia.     

The effect of head cooling on the physiological responses and resultant neural damage to global hemispheric hypoxic ischemia in prostaglandin E2 treated rats

The study determined if head cooling would reduce the augmented increase in neural damage of global hemispheric hypoxic ischemia (GHHI) of prostaglandin E2 (PGE2) treated rats. Halothane anesthetized, male, Long-Evans rats (9-11 weeks of age), kept at 37 degrees C colonically (Tc) had (a) systemic core (colonic, Tc), temporalis muscle temperatures ipsilateral (Tipsi) and contralateral (Tcontra) to the side of right common carotid artery (RCCA) ligation, (b) mean arterial pressure (MAP) and (c) ipsilateral cortical capillary blood flow (CBF) measured simultaneously after intracerebroventricular (i.c.v.) injection (2.5 microl) of sterile (SS) or 25 ng PGE2 then GHHI (35 min of 12% O2, balance N2 after RCCA ligation) followed by a 10 min normoxic recovery period. Head cooling (10 degrees C cool air over the head region) occurred in one PGE2 subgroup 10 min post-injection until the end of the hypoxic period. Icv-PGE2 treated rats, maintained at 37 degrees C (no head cooling) had increased Tc, Tipsi, Tcontras and MAPs from respective pre-injection control values; this group showed increased ipsilateral hemispheric neural damage to GHHI assessed 7 days later, compared to i.c.v.-SS treated group given the same GHHI insult. Cooling the head region of rats previously given PGE2 decreased Tipsi and Tcontras from respective control temperatures but did not change MAP or CBF from respective pre-injection values. Hemispheric damage of the PGE2 cooled group was reduced from damage of non-cooled PGE2 treated rats and was similar to i.c.v.-SS treated rats. Results demonstrate that the heightened core temperatures induced by PGE2 administration (major endogenous mediator of bacterial fever induction) play a significant role in escalating the neural damage to global ischemia.     

The effects of naloxone on cerebral blood flow and cerebral function during relative cerebral ischemia

CBF and somatosensory evoked potentials (SEPs) were measured in a model of moderate cerebral ischemia in anesthetized spontaneously hypertensive rats. The rats were bled to reduce SEP amplitudes to about 50% of prebleeding control. The consequent blood pressure fall reduced CBF to 77% of control as measured by the laser-Doppler technique. Naloxone (5 mg kg-1 i.v. plus 25 mg kg-1 h-1 i.v. for 30 min) caused a significant increase in SEP amplitudes, while CBF did not change significantly. In addition, the latency of the first SEP component decreased toward prebleeding values. Heart rate (HR) decreased, but MABP was held constant by a pressure-regulating reservoir. In unbled rats, naloxone (5 mg kg-1 i.v.) caused a transient small increase in MABP and SEP amplitudes and decrease in HR. These results indicate that sensory input is regulated by opioid systems. Increased opioid activity may inhibit ascending sensory pathways during relative cerebral ischemia and thereby depress SEP responses. Thus, naloxone can release this inhibition and enhances SEP independently of CBF during relative cerebral ischemia. Similar mechanisms might explain the apparently beneficial effects of naloxone in some stroke models.     

Fibrinolysis and aspiration of experimental intracerebral hematoma reduces the volume of ischemic brain in rats

Abstract

The hypothesis was tested in rats that brain ischemia by an intracerebral hematoma can be ameliorated by fibrinolysis and aspiration of the hematoma. Intraparenchymal blood clots were generated by the injection of 50μI of autologous blood into the right caudate nucleus in two portions seven minutes apart. Thirty or 120 min later 12 fil recombinant tissue plasminogen activator (rtPA) or 0.9% NaCI were injected and after 30 min the resolved hematoma was aspirated. Six hours later cerebral blood flow (CBF) was determined by 14C-iodoantipyrine autoradiography. Tissue volumes of CBF < 10 ml 1 00 g^–1 min-1 and CBF < 30 ml g"1 min’1 were determined. Clot and lesion volume were quantified histologically from serial sections stained for succinate-dehydrogenase (SDH) activity. In rtPA-treated rats the major part of the hematoma could be evacuated 30 min as well as 120 min after production of the clot. The volume of ischemic brain (CBF < 10) was significantly reduced fp<0.05) in the rtPA group compared to saline- treated and control groups irrespective of the time of treatment. In contrast, no difference was found between the control group and the experimental groups when the volumes of brain tissue surrounding the lesion were compared which had values of CBF<30 ml lOOgmin^–1. In a rat model of intracerebral hemorrhage, treatment by local fibrinolysis followed by aspiration of the hematoma is effective in reducing the volume of ischemic brain tissue and of the remaining clot volume. [Neurol Res 1999; 21: 517–523]     

Elevated substance-P-like immunoreactivity levels in spinal dialysates during the formalin test in normal and diabetic rats

Pharmacologic studies implicate the involvement of substance P in spinal nociceptive processing during the formalin test. However, no direct measurement of the temporal changes in substance P levels within the spinal cord of conscious animals has been reported. Further, dissociation between substance P levels and formalin-evoked nocifensive behavior may exist in diabetic rats, as exaggerated hyperalgesic behavior coexists with reduced peripheral nerve substance P levels. The present study was performed to directly measure the appearance of substance-P-like immunoreactivity (SP-LI) in spinal CSF of conscious, unrestrained rats using microdialysis techniques following injection of formalin into the hindpaw. The effect of diabetes upon formalin-evoked SP-LI levels in spinal CSF dialysates was also determined. In control rats, SP-LI increased in spinal dialysates following formalin injection and levels were maximal 20-30 min after injection, rising to 325% of basal values (p<0.02). Diabetic rats exhibited reduced (p<0.05) SP-LI in their spinal roots, while basal levels in spinal CSF were not different from controls. Formalin-evoked nocifensive behavior was increased in diabetic rats but SP-LI levels in spinal CSF dialysates after paw formalin injection were significantly (p<0.05) attenuated, reaching a maximum of only 161% of basal levels. This was accompanied by attenuated swelling at the formalin injection site and increased thermal response latencies. While increased SP-LI in spinal CSF coincides with phase 2 behavior in the formalin test and may contribute to spinal nociceptive processing during this period, exaggerated spinal substance P release is unlikely to underlie the increased nocifensive behavior seen in diabetic rats.     

Changes in monoamine neurotransmitter metabolism in brain ischemia measured by in vivo voltammetry

A preliminary work with in vivo voltammetry (IVV) in the ischemic brain had been performed by the authors in rats after cardiac arrest, which showed that the IVV system is useful to investigate ischemic brain. In the present report, IVV was applied to ischemic brain by 4-vessel occlusion in rat and changes in dopamine and serotonin metabolism were investigated by measuring peak 2 (3,4-dihydroxyphenylacetic acid, DOPAC) and peak 3 (5-hydroxyindoleacetic acid, 5-HIAA) in the striatum. The change of cerebral blood flow (CBF) were also assessed by a temperature-controlled thermoelectrical method in the striatum of the same model. The heights of peaks 2 and 3 were significantly increased to 600-900% and 200-300% respectively in the striatum during 30 minutes of 4-vessel occlusion. The increase of each peak was maximum at 10 minutes after occlusion. These changes may reflect that release of monoamine neurotransmitters is increased by the ischemia and outward transport of their metabolites are disturbed. On the other hand, after reperfusion by release of carotid occlusion, the heights of peaks 2 and 3 rapidly decreased below the control values, thereafter, peaks 2 and 3 gradually increased to over control values at 180-210 minutes after reperfusion. rCBF in the striatum decreased to almost 0 ml/100 g/min during 4-vessel occlusion ischemia and increased to over control values transiently for 30 minutes after reperfusion, followed by gradual decrease for about 240 minutes. Since monoamine neurotransmitters are known to have various effects on cerebral metabolism and CBF, their disorders may contribute to the change of CBF and the development of postischemic brain damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

A model of global forebrain ischemia/reperfusion in the awake rat.

Anesthesia is an essential element during the induction of ischemia/reperfusion and cerebral blood flow (CBF) measurement in most animal models. Cerebral neuroprotection and intrinsic effects on CBF afforded by anesthetics are confounding variables in those models. A new model of global forebrain ischemia/reperfusion (GFIR) in awake rats is presented and characterized. Rats underwent permanent occlusion of the basilar, and the paired pterygopalatine, external carotid, and occipital arteries. Inflatable balloon occluders were inserted around both common carotids, the nine-vessel occlusion (9VO) preparation. A subgroup of 9VO rats underwent placement of a laser Doppler flowmetry (LDF) probe for measurement of cortical CBF. Twenty-four hours later, while awake, 9VO rats were subjected to 10 min of ischemia by occluding both common carotid arteries. Blood gases, glucose and hematocrit were analyzed before and during ischemia, and for up to 90 min during reperfusion. Behavioral observations and continuous LDF CBF and mean arterial blood pressure determinations during ischemia and reperfusion were made. Rats were rendered comatose and decerebrate rigidity was observed during 9VO. Following balloon deflation, rats immediately regained the righting reflex and achieved complete recovery in the next 24 h. Moderate hyperglycemia was observed at 5 min of ischemia and up to 90 min reperfusion in 9VO rats. LDF CBF decreased to 5% of baseline and remained unchanged during ischemia. The 9VO is a reproducible recovery model of GFIR. Behavioral and LDF CBF correlates are consistent and survival studies are feasible.     

Measurement of somatosensory evoked potential in the Mongolian gerbil: the effects of cerebral ischaemia

Normal somatosensory evoked potential (SEP) as well as changes after incomplete cerebral ischaemia following bilateral carotid artery occlusion (BCO) were characterized in the Mongolian gerbil. BCO significantly decreased cerebral blood flow (CBF). Reperfusion CBF at 10 min and 2, 3 and 4 h was significantly below preischaemic control values. BCO decreased SEP amplitude but had no effect on EP-P₃ central conduction time. BCO did significantly increase EP-P₁₁ central conduction time. Reperfusion amplitudes at 10 min and 2, 3 and 4 h revealed a significant increase only at 4 h when compared to the ischaemic amplitude. EP-P₁₁ central conduction time at 10 min reperfusion showed dramatic improvement compared to ischaemic values, although values at 2, 3 and 4 h reperfusion were not statistically different from ischaemic values. A separate group of animals prepared identically but without BCO showed no significant changes in either SEP or CBF over time. These studies establish the protocol necessary to measure SEP in the Mongolian gerbil. In the future SEP may be used as an integral tool in the study of the primary determinants of neurophysiological recovery following cerebral ischaemia.