Prasanta Kumar Dey

Increased blood-brain barrier permeability following acute short-term swimming exercise in conscious normotensive young rats

The status of the blood-brain barrier (BBB) was examined following short-term forced swimming (FS) exercise in younger rats (age 8-9 wks, 80-90 g). Subjection of animals to continuous FS for 30 min duration increased the permeability of the BBB to Evans blue albumin (EBA) and 131I-sodium in 5 and 8 brain regions, respectively. Extravasation of the tracers was markedly pronounced in the cerebellum followed by the cerebral cortex. EBA staining was confined mainly to the posterior cingulate cortex, parietal and occipital cortices, whole cerebellar vermis and the mediolateral cerebellar cortices as well as the dorsal surface of the hippocampus. In addition to the above brain regions. BBB permeability to 131I-sodium extended to the caudate nucleus, thalamus and hypothalamus. At this time period, the serotonin (5-hydroxytryptamine, 5-HT) content showed a profound increase in plasma and brain of about 150% and 250% respectively from the control value. Pretreatment with p-CPA (p-chlorophenylalanine, a serotonin synthesis inhibitor) prevented both the increased permeability of the BBB and the rise in plasma and brain 5-HT level. However, prior treatment with cyproheptadine (a 5-HT2 receptor antagonist) prevented the increased permeability alone. The 5-HT level continued to remain high. These results suggest that short-term FS increases BBB permeability in specific brain regions. This increased permeability appears to be mediated through serotonin via 5-HT2 receptors.

Influence of long-term immobilization stress on regional blood-brain barrier permeability, cerebral blood flow and 5-HT level in conscious normotensive young rats ☆

Eight hours immobilization stress in young rats has increased the blood-brain barrier (BBB) permeability in 12 out of 14 brain regions studied. In the same regions cerebral blood flow (CBF) diminished by 2-37%, but the magnitude of flow reduction was not correlated with the degree of increased BBB permeability. On the other hand, a correlation was observed with increased plasma and brain 5-HT levels. The increased BBB permeability and increased 5-HT levels were prevented by pretreatment with p-CPA, indomethacin and diazepam. Cyproheptadine and vinblastine pretreatment prevented the occurrence of increased BBB permeability alone. The probable mechanism(s) underlying the breakdown of BBB permeability is discussed.

Influence of long-term acute heat exposure on regional blood-brain barrier permeability, cerebral blood flow and 5-HT level in conscious normotensive young rats

Exposure of conscious young rats to 4 h heat stress at 38 degrees C in B.O.D. incubator was associated with increased blood-brain barrier (BBB) permeability in 14 brain regions studied. In the same regions cerebral flow (CBF) diminished by 4-65%, but the magnitude of flow reduction was not correlated with the degree of increased BBB permeability. On the other hand, a correlation was observed with increased plasma and brain 5-hydroxytryptamine (5-HT) levels. p-Chlorophenylalanine (p-CPA), indomethacin and diazepam pretreatment prevented both the increased BBB permeability and 5-HT levels following heat exposure. Whereas cyproheptadine and vinblastine pretreatment prevented the increased BBB permeability alone. The probable mechanism(s) underlying the BBB permeability is discussed.

Changes in blood-brain barrier and cerebral blood flow following elevation of circulating serotonin level in anesthetized rats

Plasma serotonin (5-HT) was elevated by an intravenous infusion of this amine into urethane-anaesthetized rats and the concentration approximated that present in various neurological diseases and mental abnormalities. An infusion of 10 micrograms per kg body weight for 10 min significantly increased blood-brain barrier (BBB) permeability to Evans blue and 131I-sodium measured in whole brain. Regional BBB determinations with labelled 131I-sodium showed that the permeability to this compound was increased in the cerebral cortex, hippocampus, caudate nucleus, hypothalamus, colliculus and the cerebellum but not in the pons and the medulla oblongata. Regional blood flow was reduced in the same parts which showed BBB abnormality tested with 125I-labeled microspheres. Pretreatment with cyproheptadine, a 5-HT2 receptor antagonist, prevented the BBB increase and the regional blood flow was near normal values. Similar effects were obtained with indomethacin, a prostaglandin synthesis inhibitor. Vinblastine, known to influence vesicular transport, eliminated extravasation of the tracers but the regional blood flow remained depressed. A hypothesis is put forward that serotonin after binding to its receptor in the cerebral vessels stimulates prostaglandin which either directly or by means of cyclic adenosine monophosphate causes an increased vesicular transport across the endothelial cells and thus an extravasation of tracer substances in the brain. Obviously, this form of exudation can be influenced by pharmacological means.

Prostaglandins modulate alterations of microvascular permeability, blood flow, edema and serotonin levels following spinal cord injury: an experimental study in the rat.

The possibility that prostaglandins influence edema formation, microvascular permeability increase and reduction of blood flow following spinal cord trauma was examined in a rat model. In addition, the influence of prostaglandins on serotonin metabolism of the traumatized spinal cord was evaluated. Trauma to spinal cord (2-mm-deep and 5-mm-long incision in the right dorsal horn of T10-11 segments) resulted in a profound increase of the water content 5 h after injury. At this time, the microvascular permeability to Evans Blue and [131I]sodium was increased by 457 and 394%, respectively. The blood flow was reduced by 30%. The serotonin (5-hydroxytryptamine) content of the spinal cord increased by 205%. The plasma serotonin level rose by 152% in the injured group of rats. Pretreatment with indomethacin (10 mg/kg, i.p.) 30 min before trauma significantly reduced the edema and microvascular permeability increase. The local spinal cord blood flow of traumatized animals was partially restored. The increases of serotonin levels of the spinal cord and plasma were significantly attenuated. These beneficial effects of indomethacin were not present in rats given a lower dose (5 mg/kg). Indomethacin in either dose did not influence these parameters of control rats without trauma to the cord. Since indomethacin is a potential inhibitor of prostaglandins synthesis our observations indicate: (i) that prostaglandins participate in many microvascular responses (permeability changes, edema, blood flow) occurring after a trauma to the spinal cord; (ii) that these effects of the drug seem to be dose dependent, and (iii) that the prostaglandins may influence the serotonin metabolism following trauma to the spinal cord.

Histamine modulates heat stress-induced changes in blood-brain barrier permeability, cerebral blood flow, brain oedema and serotonin levels: An experimental study in conscious young rats

The possibility that endogenous histamine plays an important role in modulating the pathophysiology of heat stress was examined in young rats using a pharmacological approach. Subjection of young animals (six to seven weeks old) to heat stress at 38 degrees C for 4 h in a biological oxygen demand incubator (relative humidity 47-50%, wind velocity 20-25 cm/s) resulted in a profound increase in blood-brain barrier permeability to Evans Blue albumin (whole brain 375%) and [131I]sodium (whole brain 478%) along with a significant reduction in the cerebral blood flow (mean 34%). The water content of the whole brain was elevated by 4.5% (about 19% volume swelling) from the control. At this time-period, the plasma and whole brain 5-hydroxytryptamine levels were elevated by 656% and 328%, respectively, from the control group. Pretreatment with cimetidine (a histamine H2 receptor antagonist) significantly thwarted the increases in the brain water content and the blood-brain barrier permeability. In cimetidine-pretreated animals, the cerebral blood flow was significantly elevated and the plasma and brain 5-hydroxytryptamine (serotonin) levels were slightly but significantly reduced as compared with the untreated stressed group. However, prior treatment with mepyramine (a histamine H1 receptor antagonist) neither attenuated the changes in water content and the blood-brain barrier permeability nor altered the cerebral blood flow and 5-hydroxytryptamine levels. In fact, there was a significantly higher permeation of the tracers across the cerebral vessels in these drug-treated animals along with a greater accumulation of the brain water content as compared with the untreated stressed group. The cerebral blood flow and 5-hydroxytryptamine levels showed only minor changes from the untreated stressed group. These results show, probably for the first time, that (i) the endogenous histamine plays an important role in the pathophysiology of heat stress, and (ii) this effect appears to be mediated via specific histamine H2 receptors.

Early accumulation of serotonin in rat spinal cord subjected to traumatic injury. Relation to edema and blood flow changes.

Changes in the concentration of serotonin (5-hydroxytryptamine) in the early period after a focal traumatic injury to rat spinal cord were determined and related to the formation of edema and alterations in blood flow. A unilateral, 5-mm-long and 3-mm-deep traumatic injury located 2 mm from the midline was created in the T10-11 segment of the cord. Five hours after the injury the serotonin concentration in the traumatized segment had increased more than 100% compared with controls. There was also a progressive increase in water content of the traumatized segment measured 1-5 h after the injury. On the other hand, the spinal cord blood flow showed a progressive decrease to about 35% of its initial value at 5 h. Pretreatment with p-chlorophenylalanine, a serotonin synthesis inhibitor, impeded the elevation in water content measured 5 h after the trauma. The spinal cord blood flow remained close to normal values and the increase in serotonin was absent. Our results show that trauma to the rat spinal cord will induce changes in the serotonin concentration of the tissue and that the associated formation of edema and blood flow alterations can be alleviated in serotonin depleted rats. Obviously, serotonin plays a significant role in the pathophysiology of traumatic injury of rat spinal cord.

Evaluation of traumatic spinal cord edema using evoked potentials recorded from the spinal epidural space: An experimental study in the rat

Spinal cord evoked potentials (SCEP) elicited by simultaneous distal tibial and sural nerve stimulation were continuously recorded from the epidural space at the T9 and T12 levels of urethane anaesthetized rats before and after a unilateral incision (about 3 mm deep and 5 mm long) in the right dorsal horn of the T10-11 segments. The changes in SCEP were correlated with the increase in spinal cord water content measured 5 h after injury. In addition, the influence of serotonin (5-HT) in mediating such changes was explored using a pharmacological approach. The changes in SCEP immediately after injury correlated well with development of spinal cord edema measured 5 h after injury. Thus, the maximal negative peak (MNP) amplitude of SCEP decreased by an average of 64.0% immediately after injury and the water content of the spinal cord was increased from 71.6% (controls) to 77.6% 5 h after injury. Pretreatment with p-CPA (a serotonin synthesis inhibitor) prevented the initial decrease of the MNP amplitude and also the increase of water content (72.5%). On the other hand, pretreatment with cyproheptadine (a 5-HT2 receptor antagonist) enhanced both the initial decrease of the MNP amplitude as well as the increase of water content (81.3%). The results show a good correlation between changes of SCEP immediately after injury and the magnitude of spinal cord edema (r = 0.9) measured 5 h after injury. The findings reveal a major role of serotonin in mediating early changes of SCEP and later development of spinal cord edema and demonstrate a prognostic value of early SCEP recordings in predicting the final outcome of traumatic spinal cord injuries.

Role of histamine in traumatic brain edema: An experimental study in the rat

The possibility that histamine plays a role in the formation of traumatic brain edema was investigated in the rat. A 3 mm deep and 3 mm long stab injury was performed in the right parietal cortex under urethane anaesthesia. The brain water content and histamine levels in plasma and brain were measured at the end of 1, 2 and 5 h periods after trauma. There was a 3.46% increase in brain water content in the traumatized hemisphere from the value in the control group at 5 h. The histamine content was increased by 107% in plasma and 51% in the traumatized brain hemisphere from the control value at this time period. The increased brain water content as well as the elevated plasma and brain histamine levels were prevented by prior treatment with the histamine H2-receptor antagonist cimetidine. Mepyramine (a histamine H1-receptor antagonist) failed to reduce the increased brain water content and the histamine levels in plasma and brain remained high. The results strongly indicate that histamine has a role in the formation of early traumatic brain edema and that this reaction can be influenced by pharmacological procedures.

Opioid Receptor Antagonists Attenuate Heat Stress-Induced Reduction in Cerebral Blood Flow, Increased Blood-Brain Barrier Permeability, Vasogenic Edema and Cell Changes in the Rat

Opioid receptor antagonists attenuate heat stress-induced reduction incerebral blood flow, increased blood-brain barrier permeability, vasogenicedema and cell changes in the rat.