Combined Decompressive Hemicraniectomy and Port-Based Minimally Invasive Parafascicular Surgery for the Treatment of Subcortical Intracerebral Hemorrhage: Case Series, Technical Note, and Review of Literature.

BACKGROUND: Intracerebral hemorrhage (ICH) is a neurosurgical emergency. Combined decompressive hemicraniectomy (DHC) and minimally invasive parafascicular surgery (MIPS) may provide a practical method of managing subcortical ICH. OBJECTIVE: 1) To present a case series of combined DHC-MIPS for the treatment of subcortical-based ICH; 2) to describe technical nuances of DHC-MIPS; and 3) to provide a literature overview of MIPS for ICH. METHODS: The following inclusion criteria were used: 1) Glasgow Coma Scale (GCS) score <3-4; 2) admission within 6 hours of onset; 3) increased intracranial pressure caused by hemorrhage; 4) patient unresponsive to medical management; 5) hemorrhage >30 cm3; 6) subcortical location; and 7) midline shift (mm). Before DHC, sulcal cannulation used the following coordinates: intersection of tragus-frontal bone and midpoint of midpupillary line and midline; coronal suture: 3-4 cm posterior to this point). RESULTS: Three patients were selected: a 62-year old woman, a 45-year old woman, and a 36-year-old man. GCS and ICH scores on admission were 7 and 3, 3 and 4, and 3 and 4, respectively. ICH was located in left basal ganglia in patients 1 and 3 and right basal ganglia in patient 2, all with intraventricular extension. ICH volume was 81.7, 68.2, and 42.3 cm3, respectively. The postoperative GCS score was 11, 10, and 6, respectively. There were no intraoperative complications or mortalities. Evacuation was within 15 minutes in all patients. The modified Rankin Scale score was 3, 4, and 5, respectively, with semi-independence in case 1. CONCLUSIONS: Combined DHC-MIPS, with the use of craniometric points, can provide a unique and simple surgical option for the management of subcortical ICH.

PC-PLC/sphingomyelin synthase activity plays a central role in the development of myogenic tone in murine resistance arteries.

Myogenic tone is an intrinsic property of the vasculature that contributes to blood pressure control and tissue perfusion. Earlier investigations assigned a key role in myogenic tone to phospholipase C (PLC) and its products, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Here, we used the PLC inhibitor, U-73122, and two other, specific inhibitors of PLC subtypes (PI-PLC and PC-PLC) to delineate the role of PLC in myogenic tone of pressurized murine mesenteric arteries. U-73122 inhibited depolarization-induced contractions (high external K(+) concentration), thus confirming reports of nonspecific actions of U-73122 and its limited utility for studies of myogenic tone. Edelfosine, a specific inhibitor of PI-PLC, did not affect depolarization-induced contractions but modulated myogenic tone. Because PI-PLC produces IP3, we investigated the effect of blocking IP3 receptor-mediated Ca(2+) release on myogenic tone. Incubation of arteries with xestospongin C did not affect tone, consistent with the virtual absence of Ca(2+) waves in arteries with myogenic tone. D-609, an inhibitor of PC-PLC and sphingomyelin synthase, strongly inhibited myogenic tone and had no effect on depolarization-induced contraction. D-609 appeared to act by lowering cytoplasmic Ca(2+) concentration to levels below those that activate contraction. Importantly, incubation of pressurized arteries with a membrane-permeable analog of DAG induced vasoconstriction. The results therefore mandate a reexamination of the signaling pathways activated by the Bayliss mechanism. Our results suggest that PI-PLC and IP3 are not required in maintaining myogenic tone, but DAG, produced by PC-PLC and/or SM synthase, is likely through multiple mechanisms to increase Ca(2+) entry and promote vasoconstriction.

High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes.

BACKGROUND AND PURPOSE: Determining the role of vascular receptors in vivo is difficult and not readily accomplished by systemic application of antagonists or genetic manipulations. Here we used intravital microscopy to measure the contributions of sympathetic receptors, particularly α1-adrenoceptor subtypes, to contractile activation of femoral artery in vivo. EXPERIMENTAL APPROACH: Diameter and intracellular calcium ([Ca(2+)]i) in femoral arteries were determined by intravital fluorescence microscopy in mice expressing a Myosin Light Chain Kinase (MLCK) based calcium-calmodulin biosensor. Pharmacological agents were applied locally to the femoral artery to determine the contributions of vascular receptors to tonic contraction and [Ca(2+)]i,. KEY RESULTS: In the anesthetized animal, femoral arteries were constricted to a diameter equal to 54% of their passive diameter (i.e. tone = 46%). Of this total basal tone, 16% was blocked by RS79948 (0.1 µM) and thus attributable to α2-adrenoceptors. A further 46% was blocked by prazosin (0.1 µM) and thus attributable to α1-adrenoceptors. Blockade of P2X and NPY1 receptors with suramin (0.5 mM) and BIBP3226 (1.0 µM) respectively, reduced tone by a further 22%, leaving 16% of basal tone unaffected at these concentrations of antagonists. Application of RS100329 (α1A-selective antagonist) and BMY7378 (α1D-selective) decreased tone by 29% and 26%, respectively, and reduced [Ca(2+)]i. Chloroethylclonidine (1 µM preferential for α1B-) had no effect. Abolition of sympathetic nerve activity (hexamethonium, i.p.) reduced basal tone by 90%. CONCLUSION AND IMPLICATIONS: Tone of mouse femoral arteries in vivo is almost entirely sympathetic in origin. Activation of α1A- and α1D-adrenoceptors elevates [Ca(2+)]i and accounts for at least 55% of the tone.

Vascular tone and Ca(2+) signaling in murine cremaster muscle arterioles in vivo.

OBJECTIVES: We sought to determine some of the molecular requirements for basal state "tone" of skeletal muscle arterioles in vivo, and whether asynchronous Ca(2+) waves are involved or not. METHODS: Cremaster muscles of anesthetized exMLCK and smGCaMP2 biosensor mice were exteriorized, and the fluorescent arterioles were visualized with wide-field, confocal or multiphoton microscopy to observe Ca(2+) signaling and arteriolar diameter. RESULTS: Basal state tone of the arterioles was ~50%. Local block of Ang-II receptors (AT1 ) or α1 -adrenoceptors (α1 -AR) had no effect on diameter, nor did complete block of sympathetic nerve activity (SNA). Inhibition of phospholipase C caused dilation nearly to the Ca(2+) -free (passive) diameter, as did exposure to nifedipine or 2-APB. Arterioles were also dilated when treated with SKF96365. High-resolution imaging of exMLCK fluorescence (ratio) or GCaMP2 fluorescence in smooth muscle cells failed to reveal Ca(2+) waves (although Ca(2+) waves/transients were readily detected by both biosensors in small arteries, ex vivo). CONCLUSIONS: Arterioles of cremaster muscle have vascular tone of ~ 50%, which is not due to α1 -AR, AT1 R, or SNA. PLC activity, L-type Ca(2+) channels, 2-APB- and SKF96365-sensitive channels are required. Propagating Ca(2+) waves are not present. A key role for PLC and InsP3 R in vascular tone in vivo, other than producing Ca(2+) waves, is suggested.

Effects of siRNA knock-down of TRPC6 and InsP(3)R1 in vasopressin-induced Ca(2+) oscillations of A7r5 vascular smooth muscle cells.

We used post-transcriptional gene silencing (with small interfering RNA) to examine specifically the roles of Type 1 inositol tris-phosphate receptors (InsP(3)R1) and transient receptor potential channel 6 (TRPC6) in Ca(2+) oscillations induced by arginine vasopressin (AVP), a typical G-protein coupled receptor agonist. Ca(2+) oscillations were observed in individual A7r5 cells with confocal imaging of fluo-4 fluorescence, and SR-releasable Ca(2+) was assessed by exposure to cyclopiazonic acid (CPA). In control cells, both AVP (100 nM) and a direct activator of TRPC6 (OAG, l-oleoyl-2-acetyl-glycerol, 100 microM) caused Ca(2+) oscillations in the majority of cells (e.g. AVP: 85%, 0.97+/-0.05/min; OAG: 83%, 1.00+/-0.07/min). Partial knock-down of TRPC6 (to <27% protein expression) was more effective than partial knock-down of InsP(3)R1 (to <30% protein expression) in reducing the fraction of cells that produced Ca(2+) oscillations in response to AVP or OAG (22% and 83% of cells showing oscillations, respectively, in response to AVP; 31% and 72% of cells showing oscillation, respectively, in response to OAG). CPA-induced SR Ca(2+) release was unaffected by siRNA transfection. Inhibition of InsP(3)R with Xestospongin C abolished both AVP and OAG-induced Ca(2+) oscillations. Nifedipine (10 microM) had no effect. The key results, including the effects of partial (as opposed to complete) knock-down of InsP(3)R1 and TRPC6, and the (unexpected) finding of OAG-induced Ca(2+) oscillations, are predicted by a canonical mathematical model of Ca(2+) oscillations in which InsP(3)R1 functions as the SR Ca(2+) release channel and TRPC6 as the receptor-operated Ca(2+) influx channel. These results indicated that TRPC6 functioning as a major type of receptor-operated Ca(2+) channel played a critical role in Ca(2+) oscillations of A7r5 cells' response to AVP or OAG, and partial knock-down of TRPC6 was more effective than partial knock-down of InsP(3)R1 in reducing Ca(2+) oscillations.

A technique for simultaneous measurement of Ca2+, FRET fluorescence and force in intact mouse small arteries.

FRET (Forster resonance energy transfer)-based biosensor molecules are powerful tools to reveal specific molecular interactions in cells. Typically however, they are used in cultured cells that (inevitably) express different genes than their counterparts in intact organisms. In such cells it may be impossible to administer physiological stimuli and measure physiological outputs. Here, through the use of transgenic mice that express a FRET-based myosin light chain kinase (MLCK) biosensor molecule, we report a technique for dynamically observing activation and regulation of MLCK within the smooth muscle cells of intact, functioning small arteries, together with measurement of arterial force production and intracellular [Ca(2+)].

Ca2+ signaling in mouse mesenteric small arteries: myogenic tone and adrenergic vasoconstriction.

Arteries that have developed myogenic tone (MT) are in a markedly different physiological state compared with those that have not, with higher cytosolic [Ca(2+)] and altered activity of several signal transduction pathways. In this study, we sought to determine whether alpha(1)-adrenoceptor-induced Ca(2+) signaling is different in pressurized arteries that have spontaneously developed MT (the presumptive physiological state) compared with those that have not (a common experimental state). At 32 degrees C and intraluminal pressure of 70 mmHg, cytoplasmic [Ca(2+)] was steady in most smooth muscle cells (SMCs). In a minority of cells (34%), however, at least one propagating Ca(2+) wave occurred. alpha(1)-Adrenoceptor activation (phenylephrine, PE; 0.1-10.0 microM) caused strong vasoconstriction and markedly increased the frequency of Ca(2+) waves (in virtually all cells). However, when cytosolic [Ca(2+)] was elevated experimentally in these arteries ([K(+)] 20 mM), PE failed to elicit Ca(2+) waves, although it did elevate [Ca(2+)] (F/F(0)) further and caused further vasoconstriction. During development of MT, the cytosolic [Ca(2+)] (F/F(0)) in individual SMCs increased, Ca(2+) waves disappeared (from SMCs that had them), and small Ca(2+) ripples (frequency approximately 0.05 Hz) appeared in approximately 13% of cells. PE elicited only spatially uniform increases in [Ca(2+)] and a smaller change in diameter (than in the absence of MT). Nevertheless, when cytosolic [Ca(2+)] and MT were decreased by nifedipine (1 microM), PE did elicit Ca(2+) waves. Thus alpha(1)-adrenoceptor-mediated Ca(2+) signaling is markedly different in arteries with and without MT, perhaps due to the elevated [Ca(2+)], and may have a different molecular basis. alpha(1)-Adrenoceptor-induced vasoconstriction may be supported either by Ca(2+) waves or by steady elevation of cytoplasmic [Ca(2+)], depending on the amount of MT.

Sympathetically evoked Ca2+ signaling in arterial smooth muscle.

The sympathetic nervous system plays an essential role in the control of total peripheral vascular resistance and blood flow, by controlling the contraction of small arteries. Perivascular sympathetic nerves release ATP, norepinephrine (NE) and neuropeptide Y. This review summarizes our knowledge of the intracellular Ca2+ signals that are activated by ATP and NE, acting respectively on P2X1 and alpha1-adrenoceptors in arterial smooth muscle. Each neurotransmitter produces a unique type of post-synaptic Ca2+ signal and associated contraction. The neural release of ATP and NE is thought to vary markedly with the pattern of nerve activity, probably reflecting both pre- and post-synaptic mechanisms. Finally, we show that Ca2+ signaling during neurogenic contractions activated by trains of sympathetic nerve fiber action potentials are in fact significantly different from that elicited by simple bath application of exogenous neurotransmitters to isolated arteries (a common experimental technique), and end by identifying important questions remaining in our understanding of sympathetic neurotransmission and the physiological regulation of contraction of small arteries.

Evidence for involvement of alpha1D-adrenoceptors in contraction of femoral resistance arteries using knockout mice.

The role of alpha(1D)-adrenoceptors in vasoconstrictor responses to noradrenaline in mouse femoral resistance arteries was investigated using wire myography in alpha(1D)-adrenoceptor knockout (alpha(1D)-KO) and wild-type (WT) mice of the same genetic background.alpha(1D)-KO mice were 2.5-fold less sensitive than WTs to exogenous noradrenaline and BMY 7378 was significantly less potent against noradrenaline in alpha(1D)-KO mice than in WTs, showing a minor contribution of alpha(1D)-adrenoceptors in response to noradrenaline. Prazosin and 5-methyl-urapidil were equally effective against noradrenaline in alpha(1D)-KO and WT mice. Chloroethylclonidine produced a significantly greater attenuation of the response to noradrenaline in alpha(1D)-KO mice than in WTs. Responses to electrical field stimulation (EFS), at 2-20 Hz for 10 s and 0.09 ms pulse width were significantly smaller overall in alpha(1D)-KOs than in WTs although no significant differences were seen at the different frequencies.BMY 7378 produced significantly greater inhibition of responses at 2 and 5 Hz than at higher frequencies in WTs. In alpha(1D)-KOs, this greater sensitivity to BMY 7378 at lower frequencies was not apparent, confirming that the effect of BMY 7378 was due to blockade of alpha(1D)-adrenoceptors. Prazosin and 5-methyl-urapidil had similar inhibitory effects on responses to EFS in alpha(1D)-KO and WT mice. Chloroethylclonidine inhibited responses to EFS to a significantly greater extent in alpha(1D)-KO mice. The present study with alpha(1D)-KO mice shows that alpha(1D)-adrenoceptors contribute to vasoconstrictor responses to exogenous and neurally released noradrenaline in femoral resistance arteries.

Pharmacological characterization of alpha1-adrenoceptors in mouse isolated femoral small arteries.

Arteries were isolated from male DBA/2 mice and mounted on a small vessel wire myograph for isometric recording. Responses to exogenous noradrenaline were inhibited with high affinity by prazosin (pKB, 9.3) and 5-methyl-urapidil (pKB, 9.2) and with low affinity by 8-[2-[4-(2-methoxyphenyl)-1 piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY 7378) (pA(2), 6.7). Chloroethylclonidine (10 microM) produced only a small reduction in the maximum response to noradrenaline. Responses to electrical field stimulation were also inhibited with high affinity by prazosin (pIC50, 9.3-9.5) and 5-methyl-urapidil (pIC50, 8.0-8.3). Responses were sensitive to BMY 7378 at low frequencies of stimulation (pIC50 at 2 Hz, 8.2) but not at high frequencies (pIC50 at 20 Hz, 6.5). In conclusion, contractions to exogenous and endogenous noradrenaline in mouse femoral small arteries are mediated mainly by alpha1A-adrenoceptors. alpha1D-adrenoceptors are not involved in responses to exogenous noradrenaline but appear to be activated by neurally released noradrenaline at a low frequency of stimulation.

Alpha1-adrenoceptor subtypes involved in vasoconstrictor responses to exogenous and neurally released noradrenaline in rat femoral resistance arteries.

1. The alpha(1)-adrenoceptor subtypes involved in responses to exogenous and neurally released noradrenaline in rat femoral resistance arteries were characterised using a small vessel myograph, with antagonists prazosin (nonsubtype selective), 5-methyl-urapidil (alpha(1A)-selective), BMY 7378 (alpha(1D)-selective) and the alkylating agent chloroethylclonidine (preferential for alpha(1B)-). 2. Prazosin and 5-methyl-urapidil produced rightward shifts of the exogenous noradrenaline concentration - response curve (CRC) with pA(2) values of 9.2 and 9.1 respectively, in agreement with the presence of alpha(1A)-adrenoceptors. BMY 7378 (1 microm) shifted the noradrenaline CRC with an apparent pK(B) of 6.7, in agreement with the presence of alpha(1A)-, but not alpha(1D)-, adrenoceptors. Chloroethylclonidine at 1 microm had no effect and at 10 microm produced only a small reduction (c. 20%) in the maximum response to noradrenaline, indicating little, if any, contribution from alpha(1B)-adrenoceptors. 3. Responses of the rat femoral resistance arteries to electrical field stimulation (EFS) at 5-30 Hz for 10 s and 0.05 ms pulse width were principally due to alpha(1)-adrenoceptor stimulation. Prazosin and 5-methyl-urapidil inhibited EFS-mediated responses with pIC(50)s of 9.3 and 8.2, respectively, consistent with the alpha(1A)-adrenoceptor being the predominant subtype. Responses to EFS at 10-30 Hz were relatively insensitive to BMY 7378 (pIC(50), 6.5-6.7), while responses to 5 Hz were inhibited with a significantly higher pIC(50) of 8.02, suggesting the contribution of alpha(1D)-adrenoceptors. Chloroethylclonidine had no effect on responses to EFS, ruling out the contribution of an alpha(1B)-subtype. In the presence of cocaine, the predominant subtype involved in responses to EFS was the alpha(1A)-adrenoceptor, with a contribution from alpha(1D)-adrenoceptors at low frequency, as seen in the absence of cocaine. However, there was also a significant increase in the sensitivity to BMY 7378 at higher frequencies, suggesting that a further small alpha(1D)-adrenoceptor component may be uncovered in the presence of cocaine. 5. The present study has shown a predominant role of the alpha(1A)-adrenoceptor in contractions due to exogenous noradrenaline and to neurally released noradrenaline in rat femoral resistance arteries. alpha(1D)-Adrenoceptors are not involved in responses to exogenous noradrenaline but appear to be activated by neurally released noradrenaline at a low frequency of stimulation and at higher frequencies in the presence of neuronal-uptake blockade.