Hypercapnia produces a vasodilatation of the cerebral vasculature with an increase in cerebral blood flow and hypocapnia causes vasoconstriction with a decrease in cerebral blood flow. The cerebrospinal fluid (CSF) pressure was increased by hypercapnia and decreased by hypocapnia [1]. This suggested that the formation of CSF might be altered by carbon dioxide. However, we have seen conflicting results in regard to the influence of hypercapnia and hypocapnia on CSF formation [2][3][4][5][6]. To confirm the effects of CO 2 , we developed a new method to measure local CSF turnover rate in the lateral ventricle of the rat brain.Several methods have been developed to measure the rate of CSF production, based on (i) drainage of CSF from the cisterna magna or aqueduct; (ii) clearance of injected substances, such as inulin or dextran; and (iii) ventriculocisternal perfusion. The drainage technique was the earliest, and it was a direct attempt to measure the CSF production rate [7]. This method was applied in experiments using large animals such as dogs and cats, but it is not suitable for small animals such as rats and mice. The ventriculocisternal perfusion method [8] employs an inflow-cannula, inserted into a lateral ventricle, and an outflow-cannula in the cisterna magna. An artificial CSF is pumped in Key words: 1 H MRI, production of cerebrospinal fluid, hypocapnia, hypercapnia, carbonic anhydrase inhibitor.
Abstract:The cerebrospinal fluid (CSF) secretion of rat was monitored by longitudinal relaxation time-weighted magnetic resonance imaging (T 1 -weighted MRI) in combination with a ventricular injection of a T 1 -relaxation reagent: gadolinium-diethylene triamine-N,N,NЈ,NЉ,NЉ-pentaacetic acid (Gd-DTPA). A cannula was inserted in the left lateral ventricle, and 5 l of 8.5 mM Gd-DTPA was injected as a CSF marker. Changes in the image intensity of the CSF were measured every 30 s, and the turnover rate of CSF (k) in the left lateral ventricle was obtained from the dilution of Gd-DTPA, based on the assumption of a single compartment model. In the control conditions, k was 0.158Ϯ0.009 min Ϫ1 at an arterial blood CO 2 tension (pCO 2 ) of 38.6Ϯ2.2 mmHg (nϭ10), which corresponds to the CSF secretion rate of 3.6 l min
Ϫ1. The k value was decreased (0.078Ϯ0.010 min
Ϫ1, nϭ4) by a carbonic-anhydrase inhibitor (acetazolamide). The turnover rate was decreased by hypocapnia (0.094Ϯ0.019 min
Ϫ1, pCO 2 ϭ24.7Ϯ 2.9 mmHg, nϭ4), and it increased gradually and reached a plateau level as a result of hypercapnia (0.194Ϯ0.011 min
Ϫ1, pCO 2 ϭ104.5Ϯ7.1 mmHg, nϭ10). These results suggested that CO 2 upregulates the secretion of CSF in the rat.