Interstitial fluid movement in the brain parenchyma has been suggested to contribute to sustaining the metabolism in brain parenchyma and maintaining the function of neurons and glial cells.The pulsatile hydrostatic p...Interstitial fluid movement in the brain parenchyma has been suggested to contribute to sustaining the metabolism in brain parenchyma and maintaining the function of neurons and glial cells.The pulsatile hydrostatic pressure gradient may be one of the driving forces of this bulk flow.However,osmotic pressure- related factors have not been studied until now.In this prospective observational study,to elucidate the relationship between osmolality (mOsm/kg) in the serum and that in the cerebrospinal fluid (CSF),we simultaneously measured the serum and CSF osmolality of 179 subjects with suspected neurological conditions.Serum osmolality was 283.6 ± 6.5 mOsm/kg and CSF osmolality was 289.5 ± 6.6 mOsm/kg.Because the specific gravity of serum and CSF is known to be 1.024–1.028 and 1.004–1.007,respectively,the estimated average of osmolarity (mOsm/L) in the serum and CSF covered exactly the same range (i.e.,290.5–291.5 mOsm/L).There was strong correlation between CSF osmolality and serum osmolality,but the difference in osmolality between serum and CSF was not correlated with serum osmolality,serum electrolyte levels,protein levels,or quotient of albumin.In conclusion,CSF osmolarity was suggested to be equal to serum osmolarity.Osmolarity is not one of the driving forces of this bulk flow.Other factors such as hydrostatic pressure gradient should be used to explain the mechanism of bulk flow in the brain parenchyma.This study was approved by the Institutional Review Board of the Tohoku University Hospital (approval No.IRB No.2015-1-257) on July 29,2015.展开更多
Experimental data have shown that antiepileptic drugs cause neurodegeneration in developing rats. Valproate (VPA) is the drug of choice in primary generalized epilepsies, and carbamazepine (CBZ) is one of the most pre...Experimental data have shown that antiepileptic drugs cause neurodegeneration in developing rats. Valproate (VPA) is the drug of choice in primary generalized epilepsies, and carbamazepine (CBZ) is one of the most prescribed drugs in partial seizures. These drugs block sodium channels, thereby reducing sustained repetitive neuronal firing. The intracellular mechanisms whereby AEDs induce neuronal cell death are unclear. We examined whether AEDs induce apoptotic cell death in cultured cortical cells and whether calcium ions are involved in the AED-induced cell death. VPA and CBZ increased apoptotic cell death and induced morphological changes that were characterized by cell shrinkage and nuclear condensation or fragmentation. Incubation of cortical cultures with VPA or CBZ decreased phospho-Akt levels. CBZ decreased the intracellular calcium levels. On the other hand, FPL64176, an L-type calcium channel activator, increased the intracellular calcium levels and prevented the AED-induced apoptosis. Glycogen synthase kinase-3 inhibitors, such as alsterpaullone and azakenpaullone, prevented the AED-induced apoptosis. These results suggest that intracellular calcium level changes are associated with AEDs and apoptosis and that the activation of glycogen synthase kinase-3 is involved in the death of rat cortical neurons.展开更多
文摘Interstitial fluid movement in the brain parenchyma has been suggested to contribute to sustaining the metabolism in brain parenchyma and maintaining the function of neurons and glial cells.The pulsatile hydrostatic pressure gradient may be one of the driving forces of this bulk flow.However,osmotic pressure- related factors have not been studied until now.In this prospective observational study,to elucidate the relationship between osmolality (mOsm/kg) in the serum and that in the cerebrospinal fluid (CSF),we simultaneously measured the serum and CSF osmolality of 179 subjects with suspected neurological conditions.Serum osmolality was 283.6 ± 6.5 mOsm/kg and CSF osmolality was 289.5 ± 6.6 mOsm/kg.Because the specific gravity of serum and CSF is known to be 1.024–1.028 and 1.004–1.007,respectively,the estimated average of osmolarity (mOsm/L) in the serum and CSF covered exactly the same range (i.e.,290.5–291.5 mOsm/L).There was strong correlation between CSF osmolality and serum osmolality,but the difference in osmolality between serum and CSF was not correlated with serum osmolality,serum electrolyte levels,protein levels,or quotient of albumin.In conclusion,CSF osmolarity was suggested to be equal to serum osmolarity.Osmolarity is not one of the driving forces of this bulk flow.Other factors such as hydrostatic pressure gradient should be used to explain the mechanism of bulk flow in the brain parenchyma.This study was approved by the Institutional Review Board of the Tohoku University Hospital (approval No.IRB No.2015-1-257) on July 29,2015.
文摘Experimental data have shown that antiepileptic drugs cause neurodegeneration in developing rats. Valproate (VPA) is the drug of choice in primary generalized epilepsies, and carbamazepine (CBZ) is one of the most prescribed drugs in partial seizures. These drugs block sodium channels, thereby reducing sustained repetitive neuronal firing. The intracellular mechanisms whereby AEDs induce neuronal cell death are unclear. We examined whether AEDs induce apoptotic cell death in cultured cortical cells and whether calcium ions are involved in the AED-induced cell death. VPA and CBZ increased apoptotic cell death and induced morphological changes that were characterized by cell shrinkage and nuclear condensation or fragmentation. Incubation of cortical cultures with VPA or CBZ decreased phospho-Akt levels. CBZ decreased the intracellular calcium levels. On the other hand, FPL64176, an L-type calcium channel activator, increased the intracellular calcium levels and prevented the AED-induced apoptosis. Glycogen synthase kinase-3 inhibitors, such as alsterpaullone and azakenpaullone, prevented the AED-induced apoptosis. These results suggest that intracellular calcium level changes are associated with AEDs and apoptosis and that the activation of glycogen synthase kinase-3 is involved in the death of rat cortical neurons.
